misoprostol and Arthritis--Rheumatoid

Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Humans; Misoprostol; Musculoskeletal Diseases; Osteoarthritis; Peptic Ulcer

Rheumatic diseases often have gastrointestinal(GI) manifestations, and may present as GI bleeding and perforation due to peptic ulcer associated with high mortality. Major causes of peptic ulcer related to rheumatic diseases are drugs such as nonsteroidal anti-inflammatory drug(NSAID) and corticosteroid, and vasculitis. The analgesic effects of NSAID often mask abdominal pain until they cause GI bleeding and perforation. Therefore, it is important to make early diagnosis of peptic ulcer with upper gastrointestinal endoscope. Fundamental treatment of NSAID induced peptic ulcer is to quit it, however it is difficult because of activity of rheumatic diseases. Also, most NSAID induced peptic ulcers heal by administration of proton pump inhibitor or misoprostol. Corticosteroid pulse therapy or administration of immunosuppressant agents is effective for vasculitis induced peptic ulcer, however it is difficult to make diagnosis of it. Development of NSAID with less side effects such as cyclooxygenase-2 selective inhibitors and establishment of diagnosis and treatment of peptic ulcer related to rheumatic diseases are expected.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Histamine H2 Antagonists; Humans; Lupus Erythematosus, Systemic; Misoprostol; Omeprazole; Peptic Ulcer; Polyarteritis Nodosa; Proton Pump Inhibitors; Rheumatic Diseases

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Misoprostol; Musculoskeletal Diseases; Osteoarthritis; Pain; Peptic Ulcer; Randomized Controlled Trials as Topic; Risk; Treatment Outcome

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Humans; Misoprostol; Musculoskeletal Diseases; Osteoarthritis; Pain; Peptic Ulcer

Oral tolerance (OT) has worked well in numerous laboratory animal models of autoimmune diseases. Humans have been orally tolerized to keyhole limpet hemocyanin (KLH); patients with systemic sclerosis (SSc, scleroderma) have been orally tolerized to oral type I collagen (CI). However, clinical trials of oral type II collagen (CII) therapy in rheumatoid arthritis (RA) have had mixed results. Clinical studies show that compounds (such as nonsteroidal antiinflammatory drugs and prednisone) that inhibit generation of PGE(2) block OT induction. In murine OT models, the PGE(1) analog, misoprostol, reverses the NSAID OT block. These animal studies suggest that OT to CII or other antigens in patients with RA should be inducible if measures are taken to maintain normal prostaglandin function in the gut- associated lymphoid tissue (GALT). A clinical trial is underway in patients with RA to assess whether withholding NSAIDs and prednisone will allow OT to to be induced, and whether oral CII has meaningful clinical efficacy in this disease.

Topics: Abortifacient Agents, Nonsteroidal; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Collagen; Drug Tolerance; Humans; Immune Tolerance; Lymphoid Tissue; Misoprostol; Prednisone; Treatment Outcome

A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Gastrointestinal Diseases; Humans; Misoprostol; Osteoarthritis

This article examines the most recently published scientific literature on arthritis therapy options and available mucosal-protective agents. Emphasis is placed on the risks of current nonsteroidal anti-inflammatory drug (NSAID) therapy, the options for reducing such risks, and the published information that either supports or refutes current thinking in these areas. A comprehensive evaluation is made of clinical data related to the use of Arthrotec (diclofenac/misoprostol) in the treatment of arthritis. A recent meta-analysis of the prophylaxis of NSAID-associated upper gastrointestinal complications is reviewed. The results of this meta-analysis should help to consolidate much of the current scientific literature on the safe and effective treatment of arthritis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Diclofenac; Drug Combinations; Evidence-Based Medicine; Humans; Misoprostol

A need remains for the development of more effective therapies for the treatment of rheumatoid arthritis (both NSAIDs and DMARDs). The NSAIDs remain the cornerstone of symptomatic therapy, but concern remains about their safety, potential for the delay in commencing definitive therapy and theoretical pro-inflammatory effects. Each of the NSAIDs reviewed here do provide an advantage over therapies previously available and should prove to be useful additions to the rheumatologists' therapeutic armament.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; Cyclooxygenase Inhibitors; Cytokines; Digestive System; Drug Therapy, Combination; Humans; Indoles; Isoenzymes; Meloxicam; Misoprostol; Nabumetone; Oxindoles; Thiazines; Thiazoles

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications and are very commonly prescribed. They are used by a large proportion of elderly persons who are most prone to adverse events. NSAID gastropathy is the commonest side effect. The relative risk of adverse events is high, but the absolute risk for any individual patient is low. Individualizing the risk/benefit ratio would lead to cost effective care.

Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Duodenal Ulcer; Gastric Mucosa; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Misoprostol; Prostaglandins; Risk Factors; Sex Factors; Stomach Ulcer

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in large amounts for analgesic, antiinflammatory, and antithrombotic indications. This use is not without side effects on the gut and other organs, and some of these side effects may be serious and even lethal. No NSAID has been shown to be without side-effect potential. Use increases with age, and age poses additional risks to patients with side effects. The most serious side effects are perforation of peptic and gut ulcers and gastrointestinal (GI) bleeding, which NSAIDs, and especially acetylsalicylic acid (ASA; aspirin), may promote from both ulcer and nonulcer lesions of both the upper and lower GI tract (i.e., both acid- and nonacid-dependent). Upper GI mucosal lesions range from trivial--petechiae and superficial erosions--to significant and potentially serious deep (chronic) peptic ulcers, esophagitis, and, less commonly, small and large gut ulcers. Symptoms may occur independently of observable lesions, and serious lesions may occur without any prior symptoms. The risk of ulceration due to therapeutic doses of NSAIDs is estimated at 5- to 10-fold. NSAIDs also delay healing of conventional peptic ulcers. Moreover, ASA abuse, often surreptitious and discoverable by serum salicylate level measurement, may cause totally intractable gastric or duodenal ulceration. Surgery is contraindicated because relapse is inevitable and progressively more serious. The rational use of NSAIDs is discussed, and prophylactic and treatment strategies are proposed. None seems entirely satisfactory, and the best prophylaxis would be to avoid the use of NSAIDs except for proven indications. Until the mechanisms whereby NSAIDs both cause injury and provide therapeutic benefits can be separated, the problem of side effects and their prevention or treatment remains unresolvable.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Digestive System; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Intestinal Perforation; Intestine, Large; Intestine, Small; Misoprostol; Omeprazole; Osteoarthritis; Peptic Ulcer; Sucralfate

The results of 4 pivotal multicentre double-blind trials demonstrating the clinical efficacy of diclofenac/misoprostol in the treatment of rheumatoid and osteoarthritis are reviewed. In each study, diclofenac 50mg and diclofenac/misoprostol 50mg/200 micrograms 2 or 3 times daily were of similar therapeutic efficacy. Upper gastrointestinal endoscopy performed at baseline (day 0) and at study completion, in one study in patients with rheumatoid arthritis and one study in patients with osteoarthritis, indicated that fewer patients receiving diclofenac/misoprostol than those receiving diclofenac alone had significant erosions or ulcers at study completion. Thus, the antiarthritic efficacy of diclofenac/misoprostol was similar to that of diclofenac in the treatment of the signs and symptoms of rheumatoid and osteoarthritis, and, in addition, was associated with significantly fewer gastroduodenal mucosal erosions and ulcers than diclofenac.

Topics: Arthritis, Rheumatoid; Diclofenac; Double-Blind Method; Drug Combinations; Humans; Misoprostol; Osteoarthritis

The safety of a fixed combination of diclofenac 50mg/misoprostol 200 micrograms has been evaluated in clinical trials involving almost 2000 patients. Short term trials have been conducted in patients with osteoarthritis (n = 1032) and rheumatoid arthritis (n = 685) over 1 or 3 months. Patients randomly received either diclofenac alone or diclofenac/misoprostol. In both groups, the most frequently reported adverse events were gastrointestinal in nature, with abdominal pain reported most frequently (in 22.6% of patients receiving diclofenac/misoprostol and 19.8% of patients receiving diclofenac), followed by diarrhoea (19.5 vs 11.3%), nausea (11.0 vs 6.5%) and dyspepsia (10.6 vs 7.8%). The most frequent nongastrointestinal adverse event was headache, which occurred in 7.9% of diclofenac/misoprostol recipients and 9.3% of diclofenac recipients. Although diclofenac/misoprostol was associated with a slightly higher prevalence of adverse events than diclofenac in these studies, the majority were of mild or moderate severity, and the treatment groups were similar as regards the number of patient withdrawals resulting from adverse events. An interim analysis of the results of an ongoing trial of longer term administration of diclofenac/misoprostol (for up to 24 months) has been conducted. In this uncontrolled study, patients with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis received diclofenac/misoprostol for up to 24 months; to date 1003 patients have been enrolled and treatment has been continued for 6, 12, 18 and 24 months in 640, 327, 108 and 13 patients, respectively. As in the short term trials, the adverse events reported most commonly in this study have been predominantly gastrointestinal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arthritis, Rheumatoid; Diclofenac; Drug Combinations; Humans; Misoprostol; Osteoarthritis; Safety; Spondylitis, Ankylosing

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Constipation; Diarrhea; Diclofenac; Dizziness; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Pain; Vomiting

Although no true breakthroughs occurred, publications during the 12-month period of this review added substantial definition to certain novel immunotherapies potentially applicable to the treatment of rheumatoid arthritis. Overall, this period witnessed maturation in the field of biologic interventions. Clinical trials provided further data needed to assess the efficacy of high-dose intravenous gamma-globulin therapy in patients with systemic juvenile rheumatoid arthritis, and extended uncontrolled experience with interferon-gamma in adult rheumatoid arthritis was obtained. An intriguing immunostimulant and antiviral drug, isoprinosine (inosine pranobex), failed in a scientifically rigorous trial in rheumatoid arthritis. Provocative insights into totally new approaches surfaced in additional reports from a variety of immunologic areas. Although seemingly distal to rheumatoid arthritis, these papers are cited because their further development or adaptations could reach a stage where clinical trials in rheumatoid arthritis are warranted.

Topics: Alprostadil; Arthritis, Rheumatoid; gamma-Globulins; Humans; Immunotherapy; Inosine Pranobex; Interferon-gamma; Mechlorethamine; Methylprednisolone; Misoprostol

Nonsteroidal antiinflammatory drugs (NSAID) cause inflammation of the small intestine in 60 to 70% of patients receiving these drugs for more than 6 months. The importance of the inflammation lies in the associated complications of blood and protein loss and in the occasional development of unique small intestinal strictures requiring surgery. The pathogenesis of the inflammation is unknown. However, increased intestinal mucosal permeability due to NSAID appears to be a prerequisite; increased permeability allows exposure of the mucosa to lumenal toxins, which results in neutrophil chemotaxis and, hence, inflammation. In a study assessing the possible protective effect of misoprostol on indomethacin-induced increased small intestinal permeability, 12 volunteers underwent combined absorption/permeability tests prior to and following administration of misoprostol and/or indomethacin. Indomethacin increased intestinal permeability significantly as assessed by 51Cr-EDTA/L-rhamnose urine excretion ratio, and concomitant administration of misoprostol produced a significant protective effect. These results conform to the suggestion that NSAID-induced changes in intestinal permeability may be due to an imbalance between mucosal prostaglandins and leukotrienes. Longterm studies of the coadministration of misoprostol with NSAID are indicated to assess whether this agent reduces the severity of NSAID enteropathy.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Enteritis; Humans; Misoprostol; Osteoarthritis

Recent findings suggest that the prostaglandin E1 analog misoprostol may be associated with significant antiinflammatory and immunomodulatory effects. The addition of misoprostol to diclofenac significantly reduced the effective dose of the latter in the carrageenan acute inflammation rat model. A number of in vitro and animal studies have shown that misoprostol substantially increases the immunomodulatory effect of cyclosporine or steroids, and a study in renal transplant recipients revealed that the addition of this agent to cyclosporine and steroid treatment produced a significant improvement in renal function and a marked decrease in the incidence of graft rejection. Further, other recent data suggest that misoprostol may exert a protective effect against the damage to cartilage that appears to be induced by some nonsteroidal antiinflammatory drugs by decreasing the synthesis of cytokines. Further studies of misoprostol in these various contexts are warranted.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cartilage, Articular; Duodenal Ulcer; Humans; Kidney Transplantation; Misoprostol; Stomach Ulcer

To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions.. Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months).. Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea.. QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cohort Studies; Female; Humans; Long-Term Care; Male; Middle Aged; Misoprostol; Norway; Omeprazole; Probability; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Sickness Impact Profile; Stomach Ulcer; Stress, Psychological

To define clinically meaningful changes in 2 widely used health-related quality of life (HQL) instruments in studies of patients with rheumatoid arthritis (RA).. Patients with RA (n = 693) who were enrolled in 2 double-blind, placebo-controlled clinical trials completed the Short Form 36 (SF-36) modified health survey and the Health Assessment Questionnaire (HAQ) disability index at baseline and 6-week followup assessments. Data on 5 RA severity measures were also collected at baseline and at 6 weeks (patient and physician global assessments, joint swelling and tenderness counts, and global pain assessment). Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure.. With few exceptions, changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure. Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessments and patient pain assessment than to changes in the joint swelling and tenderness counts.. Based on these results, minimally important changes in the SF-36 scales and HAQ disability scores were determined, which will be useful in interpreting HQL results in clinical trials.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Celecoxib; Diclofenac; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Misoprostol; Pyrazoles; Quality of Life; Severity of Illness Index; Sickness Impact Profile; Sulfonamides; Surveys and Questionnaires; Treatment Outcome

1-2% of all patients under non-steroidal anti-inflammatory drug therapy are exposed to serious upper gastrointestinal complications. The policy of prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury by using misoprostol or suppressing acid secretion is still a matter of debate.. To discuss the effectiveness of prophylaxis of a gastrointestinal complication during non-steroidal anti-inflammatory drug treatment, according to the number and relevance of risk factors.. A total of 8.843 patients with rheumatoid arthritis, admitted to the widest prospective multicentre mega-trial, on 6-month complication prevention of non-steroidal anti-inflammatory drug-induced ulcers.. The results are presented in terms of the number of patients to be treated (number needed to treat) in order to prevent one serious upper gastrointestinal complication, and corrected for the number of patients, that receiving the prophylaxis therapy, would lead to one additional withdrawal (number needed to harm).. The base-line risk for a complication strongly depended on the number and relevance of risk factors: history of peptic ulcer disease, of gastrointestinal bleeding, of cardiovascular disease, and age. In the general study population, the relative risk reduction of gastrointestinal complications with misoprostol was 40%: thus the number needed to treat to prevent 1 event was 250 in the experimental period (6 months) or 125 when normalized at one-year treatment (1 year number needed to treat]. When considering the prophylaxis gain in intermediate (risk 1-2%) or high risk subjects (patients with a probability of an event over 2%, for the presence of 1 important risk factor or multiple factors), the 1-year number needed to treat rapidly drops from about 100 to about 17. The number needed to harm for one withdrawal was 18. The number needed to treat corrected for withdrawals in order to avoid major complications rises from 125 to 132 in the general population of non-steroidal anti-inflammatory drug users; from 102 to 105 in subjects at intermediate risk, such as patients with history of cardiovascular disease; in the groups at high risk, from 26 to 27 (patients with history of peptic ulcer disease), and from 16 to 17 (patients with history of peptic ulcer disease, cardiovascular disease and aged over 65 years).. Patients at intermediate and high risk for complications from non-steroidal anti-inflammatory drug-induced ulcers should be considered for prophylaxis. In this group of patients, misoprostol prevention of severe complications is effective, and its clinical relevance similar to that of other preventive measures in medical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Double-Blind Method; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Prospective Studies; Risk Factors; Stomach Ulcer

To quantify any increase in short term spontaneous ambulatory activity resulting from the use of nonsteroidal antiinflammatory drugs (NSAID) in patients with rheumatoid arthritis (RA).. Double blind placebo controlled crossover study of 8 women with RA using conventional assessments and the Numact activity monitor.. Patients' ambulatory activity was 50% greater during NSAID treatment compared to placebo treatment. Effect size calculated at 0.62, suggesting good sensitivity to change. The increased activity occurred late morning.. Spontaneous ambulatory activity is an objective and relevant measure of disability.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cross-Over Studies; Diclofenac; Double-Blind Method; Drug Combinations; Energy Metabolism; Female; Humans; Middle Aged; Misoprostol; Monitoring, Ambulatory; Outcome Assessment, Health Care; Walking

Nonsteroidal antiinflammatory drugs (NSAID), although used frequently for the treatment of arthritis and musculoskeletal disorders, may produce deleterious effects related to the gastrointestinal (GI) tract, including dyspeptic symptoms, erosions, ulcers, and serious GI complications (i.e., bleeding, perforation, and gastric outlet obstruction). Endoscopic studies with the synthetic prostaglandin E1 analog misoprostol, various acid-reducing agents (e.g., H2 receptor antagonists and proton pump inhibitors), and surface-active drugs such as sucralfate, have been shown to prevent NSAID induced gastric and/or duodenal ulcers. The Misoprostol Ulcer Complication Outcomes Safety Assessment (MUCOSA) trial was a 6 month, randomized, double blind, placebo controlled study to investigate whether concurrent administration of misoprostol would significantly reduce the occurrence of serious upper GI complications in patients with rheumatoid arthritis (RA) who were receiving NSAID. Results showed that overall complications were reduced by 40% (p = 0.049) among patients receiving misoprostol (25 patients with definite serious GI events among 4404 patients treated) compared with those receiving placebo (42 out of 4439 patients). Thus, cotherapy with misoprostol resulted in a statistically significant reduction in the incidence of serious NSAID induced upper GI complications compared with placebo in patients with RA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Double-Blind Method; Gastric Mucosa; Humans; Middle Aged; Misoprostol; Stomach Ulcer; Treatment Outcome

The fixed combination of diclofenac sodium and misoprostol (Arthrotec) is the only nonsteroidal antiinflammatory drug (NSAID) that contains a gastroprotective component and is available in 2 formulations:(1) an enteric coated core of diclofenac sodium 50 mg surrounded by a mantle of misoprostol 200 microg, and (2) a 75 mg enteric coated diclofenac core also surrounded by a 200 microg mantle of misoprostol. This article reviews the European clinical experience with both formulations in patients with arthritis.. Three randomized, blinded, multicenter studies, including one in general practice, evaluated the efficacy of combination diclofenac/misoprostol versus diclofenac or ibuprofen in a total of 1824 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Four additional studies assessed antiarthritic efficacy and employed endoscopy to compare the gastroduodenal safety of combined diclofenac50/misoprostol with that of diclofenac, naproxen, piroxicam, or indomethacin in 1459 patients with RA, OA, or ankylosing spondylitis. The gastroduodenal safety and antiarthritic efficacy of diclofenac75/misoprostol was compared with that of diclofenac in one endoscopy study involving 514 patients with RA or OA.. The efficacy and safety data obtained from these European clinical trials show that both formulations diclofenac50/misoprostol and diclofenac75/misoprostol are effective antiinflammatory drugs, with clinical efficacy equivalent to that of diclofenac. Diclofenac50/misoprostol is at least as effective as naproxen, piroxicam, indomethacin, and ibuprofen. Both formulations of the combination were associated with significantly fewer gastroduodenal ulcers compared with diclofenac. In separate studies, the tolerability of diclofenac50/misoprostol (as determined by withdrawal rates) was shown to be equivalent to that of diclofenac, naproxen, piroxicam, and ibuprofen, and the tolerability of diclofenac75/misoprostol was shown to be equivalent to that of diclofenac. The diclofenac50/misoprostol was associated with fewer decreases in hemoglobin concentration compared with diclofenac in the general practice study as well as in hospital patients.. Diclofenac50/misoprostol and diclofenac75/misoprostol are effective in treating the signs and symptoms of RA and OA and are well tolerated by the majority of patients. Both of these formulations achieve a significant reduction in the incidence of both gastric and duodenal ulcers compared with other NSAID.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Diclofenac; Double-Blind Method; Drug Combinations; Duodenal Ulcer; Duodenoscopy; Gastroscopy; Humans; Misoprostol; Naproxen; Osteoarthritis; Piroxicam; Stomach Ulcer

The aim of this study was to compare two different dosages of misoprostol (200 microg two or three times daily: MISO TID or MISO BID groups) with ranitidine (150 mg twice daily: RAN group) in the short-term prevention of acute gastroduodenal lesions induced by naproxen (500 mg twice daily).. Seventy patients (62 females, 8 males, mean age 54 yr) affected by rheumatoid arthritis (54 patients, 77%) or osteoarthritis (16 patients, 23%) with endoscopically normal mucosa were randomized to receive one of the three treatments for 2 wk. The gastroduodenal mucosa damage was scored according to a modified 0-5 endoscopic scale.. Sixty-five patients (21 of 23 patients in the MISO TID group, 22 of 23 patients in the MISO BID group, and 22 of 24 patients in the RAN group) underwent a final endoscopy, while five patients dropped out for nonmedical reasons. With intent-to-treat analysis, the percentages of significant gastric lesions was 13, 9, and 46%, respectively, for the MISO TID, MISO BID, and RAN groups (MISO TID vs RAN, p < 0.01; MISO BID vs RAN, p < 0.01). Nine patients developed an ulcer: two in the MISO TID group (one gastric ulcer and one duodenal ulcer); two in the MISO BID group (two gastric ulcers); and five in the RAN group (three gastric ulcers, one duodenal ulcer, and one patient had both gastric and duodenal ulcers).. These results show that misoprostol at 400-600 microg daily is significantly more effective than ranitidine in the short-term prevention of naproxen-induced gastric lesions. The lower dose retained mucosal protective activity that was statistically indistinguishable from that of misoprostol at 200 microg t.i.d.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Double-Blind Method; Duodenal Ulcer; Duodenum; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Naproxen; Osteoarthritis; Placebos; Ranitidine; Stomach Ulcer

This analysis evaluated the clinical and demographic risk factors for a suspected, serious nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complication in everyday clinical practice and calculated the risk reduction associated with misoprostol therapy in these "at-risk" patients.. Using logistic regression analysis, the data set from a randomized, parallel, placebo-controlled trial of misoprostol in 8,843 rheumatoid arthritis patients taking NSAIDs (the Misoprostol Ulcer Complications Outcomes Safety Assessment trial) was modeled to identify risk factors for GI adverse events. The dependent variable was defined as a "suspected serious GI complication," and the independent variables included demographic features, level of functional disability, presence of co-morbid diseases, use of certain drugs, and treatment arm.. Two hundred forty-two suspected serious GI complications were observed; 102 occurred in the misoprostol treatment group (risk: 2.32%) and 140 in the placebo group (risk: 3.15%). Overall risk reduction due to misoprostol therapy was 26.6% (confidence interval 5.5%-42.9%, P < .05). However, in patient groups with identified risk factors, misoprostol use decreased the risk for an adverse GI event by 38.3%-87.3%. Specifically, those who benefitted significantly from therapy with misoprostol were patients with a history of peptic ulcer disease (risk reduction 52.4%), history of previous GI bleeding (risk reduction 50%), history of significant cardiovascular disease (risk reduction 38.3%), significant functional disability (risk reduction 87.2%), and patients whose symptoms required concomitant antacid use (risk reduction 48.3%).. We conclude that in everyday practice, patients who require chronic NSAID therapy and who have specific clinical risk factors may benefit from misoprostol co-therapy.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Confidence Intervals; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Logistic Models; Male; Middle Aged; Misoprostol; Risk Factors; Treatment Outcome

The objective of our study was to estimate the cost effectiveness of treatment with a fixed-dose combination of diclofenac and misoprostol compared with diclofenac monotherapy in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers in rheumatoid arthritis (RA) patients. A model was used to incorporate estimates of costs, incidence of ulcers and their complications, death rates and the efficacy of misoprostol. The costs per ulcer-free period gained and costs per additional survivor were calculated. Cost effectiveness was calculated for the treatment of all RA patients, and of risk groups only. All costs were measured in 1995 Netherlands guilders (NLG; exchange rate at the time of the study: NLG1 = $US0.60). The analysis showed that if 100 RA patients receive 3 months of treatment with diclofenac plus misoprostol, instead of diclofenac alone, this will lead to overall additional costs of NLG773, while 0.82 symptomatic ulcers and 0.019 deaths will be prevented. If misoprostol is given only to patients at high risk for NSAID-induced ulcer, cost savings will occur instead of additional costs. Univariate sensitivity analysis showed that the outcomes are sensitive to changes in: (i) the percentage of ulcers treated in the ambulatory setting; (ii) the price difference between diclofenac and the fixed-dose diclofenac-misoprostol combination; (iii) the percentage of ulcers with complications; and (iv) the efficacy of misoprostol. In conclusion, it can be stated that treatment with diclofenac-misoprostol is cost saving in RA patients at high risk for NSAID-induced ulcers. For RA patients in general, the cost-effectiveness of this intervention compares favourably with that of other prophylactic treatments.

Topics: Age Factors; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Diclofenac; Drug Combinations; Humans; Misoprostol; Models, Economic; Peptic Ulcer

To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs).. 6-month randomized, double-blind, placebo-controlled trial.. 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.. 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993.. Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.. Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy).. Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months.. In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Misoprostol; Odds Ratio; Risk Factors

The objective of this study was to determine the long-term efficacy of misoprostol in preventing diclofenac-induced gastroduodenal ulcers in rheumatoid arthritis and osteoarthritis patients. Three hundred eighty-four patients who had an endoscopically confirmed gastric or duodenal lesion that had healed with misoprostol therapy were randomized to receive misoprostol or placebo coadministered with diclofenac for up to 52 weeks. Endoscopic examinations were repeated at weeks 12, 24, and 52. The development of a gastric and/or duodenal ulcer was considered a prophylaxis failure. Results in the evaluable cohort of patients demonstrated that gastroduodenal ulcer incidences were lower with misoprostol than placebo for all study periods (0-12 weeks, 7% vs 23%; 0-24 weeks, 11% vs 26%; and 0-52 weeks, 15% vs 31%). Misoprostol did not interfere with the antiarthritic effects of diclofenac. In conclusion, misoprostol coadministered with diclofenac for 12 months to patients with rheumatoid arthritis or osteoarthritis significantly reduced the incidence of diclofenac-induced gastroduodenal ulcers (P < or = 0.018).

Topics: Arthritis, Rheumatoid; Diclofenac; Endoscopy, Gastrointestinal; Female; Humans; Incidence; Life Tables; Male; Middle Aged; Misoprostol; Osteoarthritis; Peptic Ulcer; Time Factors

A double-blind, randomised, parallel-group study was conducted in eight countries to compare the efficacy of a fixed combination of diclofenac sodium (50 mg) and misoprostol (200 mcg) with a fixed combination of diclofenac sodium (50 mg) and placebo in treating the signs and symptoms of rheumatoid arthritis (RA). A total of 346 patients with RA who had been stabilised on diclofenac for at least 30 days were randomly assigned to receive either diclofenac/misoprostol BID or TID (n = 177) or diclofenac/placebo BID or TID (n = 169) for 12 weeks. Primary analyses of efficacy, made upon admission and at 4-week intervals, consisted of physician's global assessment of the arthritic condition, patient's global assessment of the arthritic condition, patient's global assessment of joint tenderness/pain, and physician's assessment of joint swelling. In this study, the fixed combination tablet of diclofenac sodium 50 mg/misoprostol 200 mcg administered BID or TID demonstrated no statistically significant difference in efficacy in the treatment of the signs and symptoms of RA compared with diclofenac sodium 50 mg/placebo administered BID or TID.

Topics: Arthritis, Rheumatoid; Cohort Studies; Diclofenac; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Tablets, Enteric-Coated

To assess whether the synthetic prostaglandin misoprostol is renal protective in rheumatoid arthritis (RA) patients who are beginning cyclosporin A (CSA) therapy.. In this randomized, placebo-controlled, multicenter trial, 50 patients with active RA were randomized to receive either misoprostol (800 micrograms/day) or placebo for 16 weeks. After 2 weeks of pretreatment with misoprostol or placebo, all patients concomitantly received CSA at an initial and maximum dosage of 5 mg/kg/day for 12 weeks.. A significant increase in the serum creatinine level was observed in both treatment groups, with no difference noted between groups. There was a high withdrawal rate in both groups, primarily due to adverse events.. A renal-protective effect was not demonstrated for misoprostol compared with placebo in RA patients who are beginning CSA therapy.

Topics: Adult; Aged; Arthritis, Rheumatoid; Cyclosporine; Female; Gastrointestinal Diseases; Humans; Hypertension; Kidney; Kidney Diseases; Male; Middle Aged; Misoprostol; Placebos; Prospective Studies

The objective of this study is to utilize a clinical trial based on a decision-analysis model to assess the economic benefit of a lower incidence of gastrointestinal lesions in elderly patients with osteoarthritis receiving nabumetone therapy compared with ibuprofen alone and in combination with misoprostol. An arthritic population of an HMO (> 60 yr of age) was applied to the decision analysis based on the HMO's nonsteroidal anti-inflammatory drug and antiulcer usage and acquisition costs. Results indicate the potential for a decrease in overall medical resource utilization through the use of nabumetone in elderly patients with rheumatoid and osteoarthritis. Based on this information, nabumetone has been added to the HMO formulary as a second-tier agent with a repeat of the analysis scheduled in one year to verify the economic benefits and modify prescribing guidelines accordingly.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; Decision Trees; Drug Therapy, Combination; Formularies as Topic; Gastrointestinal Diseases; Health Maintenance Organizations; Humans; Ibuprofen; Incidence; Middle Aged; Misoprostol; Models, Economic; Northwestern United States; Osteoarthritis

The results of 4 pivotal multicentre double-blind trials demonstrating the clinical efficacy of diclofenac/misoprostol in the treatment of rheumatoid and osteoarthritis are reviewed. In each study, diclofenac 50mg and diclofenac/misoprostol 50mg/200 micrograms 2 or 3 times daily were of similar therapeutic efficacy. Upper gastrointestinal endoscopy performed at baseline (day 0) and at study completion, in one study in patients with rheumatoid arthritis and one study in patients with osteoarthritis, indicated that fewer patients receiving diclofenac/misoprostol than those receiving diclofenac alone had significant erosions or ulcers at study completion. Thus, the antiarthritic efficacy of diclofenac/misoprostol was similar to that of diclofenac in the treatment of the signs and symptoms of rheumatoid and osteoarthritis, and, in addition, was associated with significantly fewer gastroduodenal mucosal erosions and ulcers than diclofenac.

Topics: Arthritis, Rheumatoid; Diclofenac; Double-Blind Method; Drug Combinations; Humans; Misoprostol; Osteoarthritis

The safety of a fixed combination of diclofenac 50mg/misoprostol 200 micrograms has been evaluated in clinical trials involving almost 2000 patients. Short term trials have been conducted in patients with osteoarthritis (n = 1032) and rheumatoid arthritis (n = 685) over 1 or 3 months. Patients randomly received either diclofenac alone or diclofenac/misoprostol. In both groups, the most frequently reported adverse events were gastrointestinal in nature, with abdominal pain reported most frequently (in 22.6% of patients receiving diclofenac/misoprostol and 19.8% of patients receiving diclofenac), followed by diarrhoea (19.5 vs 11.3%), nausea (11.0 vs 6.5%) and dyspepsia (10.6 vs 7.8%). The most frequent nongastrointestinal adverse event was headache, which occurred in 7.9% of diclofenac/misoprostol recipients and 9.3% of diclofenac recipients. Although diclofenac/misoprostol was associated with a slightly higher prevalence of adverse events than diclofenac in these studies, the majority were of mild or moderate severity, and the treatment groups were similar as regards the number of patient withdrawals resulting from adverse events. An interim analysis of the results of an ongoing trial of longer term administration of diclofenac/misoprostol (for up to 24 months) has been conducted. In this uncontrolled study, patients with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis received diclofenac/misoprostol for up to 24 months; to date 1003 patients have been enrolled and treatment has been continued for 6, 12, 18 and 24 months in 640, 327, 108 and 13 patients, respectively. As in the short term trials, the adverse events reported most commonly in this study have been predominantly gastrointestinal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arthritis, Rheumatoid; Diclofenac; Drug Combinations; Humans; Misoprostol; Osteoarthritis; Safety; Spondylitis, Ankylosing

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Therapy, Combination; Humans; India; Misoprostol; Osteoarthritis; Pilot Projects; Stomach Ulcer; Treatment Outcome

Indomethacin, a nonsteroidal anti-inflammatory drug, may cause gastric mucosal damage as shown by fecal blood loss. A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the effects of 400 mcg b.i.d. misoprostol, a synthetic prostaglandin E1 analog, on intestinal blood loss caused by 50 mg t.i.d. indomethacin. Forty-two arthritic patients, mean age 59 years, received indomethacin for 14 days. Those with baseline blood loss of at least 1.5 ml/day during the first 7 days were randomized to 400 mcg of misoprostol or placebo (days 8 to 14). Fecal blood loss was measured using 51Cr labelled red blood cell technique. Success was defined as a reduction in mean daily blood loss of at least 50% during the treatment period compared to mean daily blood loss during the baseline (pre-treatment) phase. The mean daily blood loss on treatment days 9-15 was not significantly reduced from baseline in either group. These data neither confirm nor deny the effectiveness of misoprostol in reducing fecal blood loss caused by indomethacin. The results may have been confounded by the administration of misoprostol twice daily while indomethacin was administered three times daily. In addition, fecal blood loss as an indicator of gastrointestinal mucosal damage is not a sensitive measure; it is characterized by poor reproducibility and wide fluctuations within individual responses. Inappropriate laboratory techniques may have further reduced the sensitivity and reliability of this procedure.

Topics: Arthritis, Rheumatoid; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Humans; Indomethacin; Male; Middle Aged; Misoprostol; Occult Blood; Osteoarthritis; Treatment Outcome

Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.

Topics: ABO Blood-Group System; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Duodenum; Female; Gastric Acid; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Peptic Ulcer

Two double-blind comparative studies were conducted to determine the upper gastrointestinal safety of Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol versus 50 mg of diclofenac. In one study, rheumatoid arthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 12 weeks. Endoscopy was performed before and after treatment. At the termination of treatment, among the 290 patients with rheumatoid arthritis, gastroduodenal ulcers were found in 4% of the Arthrotec-treated patients and in 11% of the diclofenac-treated patients (P = 0.034). In the second study, osteoarthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 4 weeks. Endoscopy was performed before and after treatment. Among the 329 patients with osteoarthritis, gastroduodenal ulcers were found in none of the Arthrotec patients and in 4% of the diclofenac patients (P = 0.015).

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Diclofenac; Digestive System; Double-Blind Method; Drug Combinations; Endoscopy; Female; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Male; Middle Aged; Misoprostol; Osteoarthritis

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Constipation; Diarrhea; Diclofenac; Dizziness; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Pain; Vomiting

In a double-blind study, 346 patients with active rheumatoid arthritis were randomly assigned to receive Arthrotec, a combination of 50 mg of diclofenac and 200 *g of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 12 weeks. At weeks 4, 8, and 12 of treatment, no clinically significant differences between the two treatment groups were noted on measures of joint tenderness, pain, and swelling or on physicians' and patients' assessments of disease severity.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Diclofenac; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Misoprostol

This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Diclofenac; Digestive System; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Misoprostol; Stomach Ulcer

We assessed the effect of the prostaglandin E1 analog misoprostol on cyclosporine nephrotoxicity in patients with rheumatoid arthritis (RA). Thirteen patients with RA were given cyclosporine with misoprostol tablets, 800 micrograms/day for one week in a randomized, double blind, placebo controlled crossover trial. All had cyclosporine nephrotoxicity, documented by an increase in serum creatinine of at least 15% over the values before the start of cyclosporine treatment. Mean glomerular filtration rate (GFR) (single shot 51Cr-EDTA plasma clearance) at baseline was 77.3 ml/min (SD, 22.0). After misoprostol, it was 80.0 ml/min (SD, 18.9); after placebo, 79.1 ml/min (SD, 20.0). None of these changes were statistically significant. Serum creatinine levels and whole blood cyclosporine levels were also unchanged. Power to detect at least a 5 ml/min rise in GFR was 0.92. Short term misoprostol treatment does not improve the GFR of patients with RA on cyclosporine.

Topics: Adult; Arthritis, Rheumatoid; Cyclosporine; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Misoprostol; Time Factors

The cytoprotective effect of misoprostol co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) was assessed in a double blind, placebo controlled study. Thirty-seven patients with rheumatoid arthritis receiving NSAIDs, having upper gastrointestinal symptoms and endoscopically confirmed gastric and/or duodenal lesions, were randomised to receive either misoprostol 200 micrograms or placebo tablets twice daily for 4 weeks. Of 31 evaluable cases, 13 of 16 (81%) patients receiving misoprostol showed endoscopic improvement as compared to 10 of 15 (67%) receiving placebo (P:NS). A significant decrease in mean (+/- SEM) mucosal lesion score was observed with misoprostol (from 3.38 +/- 0.32 to 1.32 +/- 0.44; P less than 0.001) but no change was seen with placebo (from 2.80 +/- 0.42 to 1.60 +/- 0.53; P:NS). Symptomatic relief was similar in both groups, being 44% and 40% respectively. Two patients complained of diarrhea in each group and one developed menorrhagia with misoprostol. It is concluded that though misoprostol decreased the number of NSAID-induced mucosal lesions, it was unable to relieve gastrointestinal symptoms.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Misoprostol

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Duodenal Ulcer; Female; Gastric Mucosa; Humans; Japan; Male; Middle Aged; Misoprostol; Stomach Ulcer; Time Factors

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Evaluation; Duodenal Ulcer; Female; Humans; Japan; Male; Middle Aged; Misoprostol; Stomach Ulcer; Time Factors

Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Humans; Male; Misoprostol; Osteoarthritis; Peptic Ulcer; Spondylitis, Ankylosing

Non-steroidal anti-inflammatory drugs can reversibly decrease renal function in patients with rheumatoid arthritis (RA). To test whether orally administered prostaglandins could mitigate this decrease, we studied the effect of misoprostol in 24 RA patients during treatment with diclofenac in a randomized, placebo-controlled crossover trial. At baseline, 21 patients had a creatinine clearance below 80 ml/min/1.73 m2. The two treatment phases (with either misoprostol, 600 micrograms daily, or matching placebo tablets) were separated by a washout phase in which diclofenac (150 mg daily) was continued. After treatment with misoprostol/diclofenac the glomerular filtration rate was 72 +/- 5 ml/min (mean +/- standard error), and the effective renal plasma flow was 295 +/- 21 ml/min. After treatment with placebo/diclofenac, the corresponding values were 71 +/- 5 ml/min and 296 +/- 21 ml/min, respectively. We concluded that misoprostol has no effect on the renal function of RA patients treated with diclofenac.

Topics: Adult; Aged; Alprostadil; Arthritis, Rheumatoid; Creatinine; Diclofenac; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Misoprostol; Severity of Illness Index

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Aspirin; Humans; Misoprostol; Peptic Ulcer

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis. Patients with confirmed rheumatoid arthritis and endoscopically documented gastroduodenal lesions were randomly assigned to receive 200 micrograms of misoprostol four times a day (123 patients) or placebo (116 patients). Each concurrently received 650 to 1300 mg of aspirin four times a day. After eight weeks of treatment, misoprostol was statistically superior to placebo in healing gastric mucosal injury (70% vs 25%) and duodenal mucosal injury (86% vs 53%). Patients with gastric or duodenal ulcers on admission had superior ulcer healing rates with misoprostol (67% vs 26%). There was no evidence of interference with the antirheumatic properties of aspirin. Mild to moderate adverse experiences were equally noted in misoprostol and placebo groups. Misoprostol, coadministered with aspirin, is well tolerated and highly effective in healing aspirin-associated gastroduodenal lesions in patients with rheumatoid arthritis without altering the therapeutic benefits of aspirin.

Topics: Adult; Aged; Alprostadil; Anti-Ulcer Agents; Arthritis, Rheumatoid; Aspirin; Double-Blind Method; Duodenoscopy; Female; Gastroscopy; Humans; Male; Middle Aged; Misoprostol; Multicenter Studies as Topic; Peptic Ulcer; Random Allocation

Topics: Adult; Alprostadil; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Double-Blind Method; Duodenal Ulcer; Gastroscopy; Humans; Indomethacin; Misoprostol; Omeprazole; Prostaglandins E; Ranitidine; Rioprostil; Stomach Ulcer

Acid suppressants such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are effective in preventing gastrointestinal (GI) bleeding in nonsteroidal anti-inflammatory drugs (NSAIDs) users. Despite widespread acid suppressant use, there remain concerns about several potential risks of long-term use. Therefore, we investigated whether gastroprotective agents (GPAs) other than acid suppression therapy are effective in preventing NSAID-related GI injury. To this end, we studied 9,133 patients with osteoarthritis or rheumatoid arthritis who used NSAIDs for ≥1 month. A decrease of 2 g/dL or more in the hemoglobin level was considered a GI injury indicator. The GPAs included acid suppressants and other mucoprotective agents. Acid suppressants included PPIs and H2RAs. Other mucoprotective agents included misoprostol, rebamipide, and eupatilin. During a median follow-up period of 27 (range, 4.3-51.3) weeks, occult GI bleeding occurred in 1,191 (13%) patients. A comparison of patients who used GPAs concomitantly with that of nonusers in a multivariable analysis revealed the hazard ratios (HRs; 95% confidence intervals [CIs]) for occult GI bleeding were 0.30 (0.20-0.44), 0.35 (0.29-0.43), 0.47 (0.23-0.95), 0.43 (0.35-0.51), and 0.98 (0.86-1.12) for PPIs, H2RAs, misoprostol, rebamipide, and eupatilin, respectively. Compared to PPI co-treatment, H2RA, misoprostol, rebamipide, and eupatilin co-treatments were associated with occult GI bleeding HRs (95% CIs) of 1.19 (0.79-1.79), 1.58 (0.72-3.46), 1.44 (0.96-2.16), and 3.25 (2.21-4.77), respectively. Our findings suggest that mucoprotective agents, such as rebamipide and misoprostol, as well as acid suppressants, are effective in reducing the risk for GI injury in NSAID users.

Topics: Adult; Aged; Alanine; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cohort Studies; Female; Flavonoids; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemoglobins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Misoprostol; Osteoarthritis; Proton Pump Inhibitors; Quinolones; Treatment Outcome

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cooperative Behavior; Deglutition Disorders; Diagnosis, Differential; Diclofenac; Drug Therapy, Combination; Dysphonia; Endoscopy; Female; Folic Acid; Humans; Interdisciplinary Communication; Lymphopenia; Methotrexate; Middle Aged; Misoprostol; Opportunistic Infections; Oral Ulcer; Pain; Pharyngitis; Prednisolone

The objective was to assess the cost-effectiveness of nonsteroidal anti-inflammatory agents (NSAIDs), NSAIDs with concomitant therapy to prevent gastrointestinal (GI) toxicity, and cyclooxygenase-2 specific inhibitors (COX-2) in the treatment of rheumatoid arthritis (RA). Markov (state-transition) models were used to simulate a cohort taking disease-modifying antirheumatic drugs, low dose steroid, and one of the following strategies: (1) NSAIDs without prophylaxis, (2) NSAIDs with misoprostol, (3) NSAIDs with proton-pump inhibitor (PPI), or (4) COX-2. Costs were measured in 1999 US dollars and health effects are expressed as quality-adjusted life years (QALYs). COX-2 was the most cost-effective strategy for preventing GI toxicity. The incremental cost/effectiveness (C/E) ratio between COX-2 and no prophylaxis was 56,751 dollar/QALY. Although COX-2 are the best option (among the strategies analyzed) to prevent GI toxicity, the incremental C/E ratio between COX-2 and no prophylaxis is higher than 50,000 dollar/QALY.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Gastrointestinal Diseases; Markov Chains; Misoprostol; Omeprazole; Proton Pump Inhibitors

The objective of this study was to evaluate the potential economic implications of using etoricoxib versus non-selective NSAID alternatives in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in the UK.. Decision-analytical modelling was used to calculate the expected costs and consequences of the use of etoricoxib compared with non-selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous treatment period of 1 year.. The model considered direct medical costs from the perspective of the UK National Health Service (NHS) and used data from phase IIb and III clinical trials of etoricoxib to determine probabilities of gastrointestinal (GI) events. Model outcomes were defined as resource-consuming GI-related events, including clinically evident gastroduodenal perforations, symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002 values) for the treatment of OA and RA as well as GI events were based on published literature and information available from UK-specific sources.. The model suggests that etoricoxib is cost saving compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus misoprostol. The model also suggests that etoricoxib is cost effective in terms of the incremental cost per QALY gained for non-selective NSAIDs alone (pound 19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non-selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2 antagonists. For patients without the presence of specific GI risk factors (history of GI event, corticosteroid use or disability), etoricoxib may be cost effective for patients over age 56 years, assuming a cost-effectiveness threshold of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in patients of all ages who had at least one specific GI risk factor.. The model suggests, with its underlying assumptions and data, that etoricoxib is a cost-effective alternative to therapeutic regimens involving non-selective NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving and dominant over non-selective NSAIDs used together with a PPI or misoprostol. When compared with non-selective NSAIDs alone or non-selective NSAIDs co-prescribed with H2 antagonists, the incremental cost per QALY gained with use of etoricoxib was within the generally accepted threshold for cost effectiveness (less than pound 30,000 per QALY gained).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cost-Benefit Analysis; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Etoricoxib; Gastrointestinal Diseases; Histamine H2 Antagonists; Humans; Middle Aged; Misoprostol; Models, Economic; Osteoarthritis; Proton Pump Inhibitors; Pyridines; Quality-Adjusted Life Years; Risk; Sulfones; Time Factors; United Kingdom

To determine the extent of evidence based practice among rheumatologists in the prevention of nonsteroidal antiinflammatory drug (NSAID) associated peptic ulcer disease and to seek ways to improve the management of high risk NSAID users.. In March 1996 all 7 rheumatologists from Saskatoon participated in a consensus conference to develop local guidelines for the prophylaxis of NSAID associated peptic ulcer disease. We performed a retrospective chart review for September/October 1995 (baseline) and for June/July 1996 (post-consensus guideline) of all patients from Saskatoon rheumatologists who were being treated with NSAID for either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis (IP). A prospective crossover intervention study was performed from January to April 1997 in which 2 subgroups of rheumatologists (university or private practice) had a reminder sheet of gastrointestinal (GI) bleeding risk assessment placed into the front of each patient's chart prior to each office visit. The GI bleeding risk for each patient at time of visit was later determined by chart review. The primary outcome was the proportion of adherence to guidelines for high risk NSAID users in the combined intervention group (reminder sheet) compared to the combined control group (no reminder sheet) in the prospective controlled crossover study.. A total of 484 patients with RA or IP received NSAID during the 4 study periods. Of these, 82 patients (16.9%) were at high risk of GI bleed. In 1995, the proportion of high risk patients taking misoprostol was 29% for university and 33% for private practice rheumatologists. The establishment of local consensus guidelines in 1996 temporarily increased adherence to guidelines to 43%, but only for private practice rheumatologists. During the prospective study, adherence to guidelines was significantly greater in the intervention (reminder sheets) group compared to the control (no reminder sheets) group (53% vs 15%; p = 0.014).. The simple intervention of reminder sheets for GI bleeding risk assessment resulted in a significant increase in rheumatologists' adherence to guidelines, although a substantial number of patients remained untreated with misoprostol. This study illustrates the difficulty of incorporating new knowledge and recommendations into clinical practice. Additional strategies should be investigated to more effectively incorporate new knowledge in the practice of rheumatology.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Female; Guideline Adherence; Humans; Male; Middle Aged; Misoprostol; Peptic Ulcer; Professional Practice; Prospective Studies; Reminder Systems; Rheumatology; Risk Assessment

To try arthrotek, a combined drug, in patients with rheumatoid arthritis (RA).. 10 RA women aged 30 to 60 years with endoscopically verified minimal affection of gastroduodenal mucosa (not more than 25 hemorrhages and/or 5 erosions) received arthrotek (1 tablet 3 times a day for 3 months). The efficacy was judged by changes in the joints and gastroduodenal lesions.. The 3-month treatment produced positive changes in the main auricular and gastroduodenal symptoms. Side effects (head ache, diarrhea, sleepiness) disappeared after reducing the day dose to 2 tablets.. Arthrotek proved highly effective against RA. It is also a good gastroprotector promoting healing of gastroduodenal erosions.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diclofenac; Drug Combinations; Endoscopy, Digestive System; Female; Gastric Mucosa; Humans; Middle Aged; Misoprostol; Treatment Outcome

To carry out a economic evaluation of diclofenac/misoprostol in the treatment of rheumatoid arthritis and osteoartritis when comparing with diclofenac alone, diclofenac + omeprazol, and diclofenac + ranitidine.. Cost effectiveness analysis using a decision analytic model, where the effectiveness unit was defined as the patient free of gastro-intestinal toxicity.. The effectiveness data of the four alternatives under evaluation have been obtaining from published clinical trials. In this analysis only direct medical costs have been included without incorporating indirect costs or intangible costs. The perspective chosen has been a primary care area and the time horizon 6 months. All costs are expressed in monetary units of 1998.. The cost/effectiveness ratio obtained with diclofenac/misoprostol has been a 37% lower compared with diclofenac alone (42,238 vs 67,214 ptas), a 39% compared with diclofenac + omeprazol (42,238 vs 69,058 ptas) and a 50% compared with diclofenac + ranitidine (42,238 vs 85,198 ptas). The sensitivity analysis performed has shown that diclofenac/misoprostol is the therapeutic alternative more efficient even when most influential variables are modified.. Diclofenac/misoprostol has demonstrated to be an alternative with a better cost/effectiveness ratio, and therefore more efficient than diclofenac alone or the concomitant use of diclofenac either with omeprazol or ranitidine. The routinary use of this association will save important resources to the National Health Service.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Decision Trees; Diclofenac; Gastrointestinal Diseases; Humans; Misoprostol; Omeprazole; Osteoarthritis; Ranitidine

To estimate the costs and health consequences of replacing treatment with diclofenac 50 mg with a fixed combination of diclofenac 50 mg and misoprostol 0.2 mg 3 times a day in patients with rheumatoid arthritis (RA).. A decision tree was developed to simulate 6 months of nonsteroidal antiinflammatory drug (NSAID) treatment for RA. The probabilities of the clinical outcomes were based on a literature review. A survey of Norwegian rheumatologists was undertaken to explore their clinical management of dyspepsia in RA patients taking NSAIDs. Valuation of health states was based on results of the Short Form 36 health survey.. In female RA patients without any risk factors associated with serious gastrointestinal (GI) complications, the incremental cost of replacing diclofenac with the fixed misoprostol/diclofenac combination therapy was $72,700 per quality-adjusted life-year gained. For patients with 1 risk factor, the cost was less than $16,000. With 2 or 3 risk factors, the use of misoprostol was cost saving. The cost-effectiveness ratios in males were approximately 20% higher than in females.. Replacing diclofenac with a fixed diclofenac/misoprostol combination is cost effective when restricted to RA patients at increased risk of serious GI events.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Diclofenac; Drug Therapy, Combination; Female; Gastric Mucosa; Health Status; Humans; Misoprostol

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis; Arthritis, Rheumatoid; Duodenal Ulcer; Female; Histamine H2 Antagonists; Humans; Male; Misoprostol; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Ranitidine; Research; Stomach Ulcer; Time Factors

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Humans; Misoprostol; Stomach Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Costs; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cost-Benefit Analysis; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cost-Benefit Analysis; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Misoprostol

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Misoprostol

To determine the cost-utility of low-dose misoprostol prophylaxis in rheumatoid arthritis (RA) patients treated with nonsteroidal antiinflammatory drugs (NSAIDs).. Prospectively collected, population-based data on 57 RA patients' preferences (obtained using the category scaling and time trade-off techniques), charge data from a consecutive, population-based cohort of 36 RA patients with NSAID-related gastric ulcer, and literature-derived probability estimates were incorporated into a decision analysis model.. Probabilistic sensitivity analysis using 10,000 Monte Carlo simulations demonstrated that, on average, prophylaxis resulted in modest additional costs and no additional quality-of-life benefits. At best, the incremental cost per quality-adjusted life year gained was $9,333. At worst, prophylaxis reduced quality of life. Prophylaxis was cost-saving if the ulcer complication rate was > 1.5%, or if the 3-month price of misoprostol was < or = $95.. Whereas prophylaxis may be cost-saving among high-risk NSAID users, from some patients' perspective, it reduces quality of life. Although these data may not be generalizable to other clinical populations, they illustrate the importance of incorporating patient preferences into economic evaluations.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cost-Benefit Analysis; Decision Support Techniques; Decision Trees; Female; Humans; Male; Middle Aged; Misoprostol; Monte Carlo Method; Patient Satisfaction; Probability; Prospective Studies; Quality of Life; Sensitivity and Specificity; Stomach Ulcer

We conducted a pilot study examining the relative preferences for various nonsteroidal antiinflammatory drug associated adverse gastrointestinal events and misoprostol prophylaxis for these events. Thirty patients with rheumatoid arthritis volunteered to participate. A trained nurse interviewer administered the structured pretested interview. Respondents rated 18 hypothetical health states on a category rating scale with anchors at 0 (immediate death) and 100 (full health for life). Linear contrasts were created to test the null hypotheses of equal preferences, using t tests for correlated means. Our results suggest that respondents place a high value on the avoidance of (in order of decreasing importance) surgery, hospitalization, prophylaxis induced diarrhea and uncomplicated ulcer requiring outpatient treatment. The avoidance of ulcer symptoms (primarily dyspepsia) and the inconvenience of an additional medication taken 4 times daily (in the absence of diarrhea) appeared to be substantially less important from these patients' perspective. Further work is underway to confirm these preliminary findings.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diarrhea; Female; Humans; Male; Middle Aged; Misoprostol; Patient Participation; Pilot Projects; Stomach Ulcer

A patient with rheumatoid arthritis, who also had documented achlorhydria, first had the diagnosis of an antral ulcer made by barium meal in 1980. She did well taking cimetidine intermittently after that, along with various nonsteroidal antiinflammatory drugs (NSAIDs). In 1988, a shallow antral ulcer was found, but the patient did not respond to H2 blockade or to sucralfate. At that time misoprostol therapy was prescribed. Despite the continued use of NSAIDs, the ulcer healed. It has remained healed for the past 3 years.

Topics: Achlorhydria; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Chronic Disease; Female; Gastric Acidity Determination; Humans; Misoprostol; Pentagastrin; Stomach Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diclofenac; Drug Combinations; Gastrointestinal Diseases; Humans; Misoprostol; Osteoarthritis; Rheumatic Diseases

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Duodenal Ulcer; Gastric Mucosa; Humans; Intestinal Mucosa; Misoprostol; Stomach Ulcer

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Female; Humans; Misoprostol; Peptic Ulcer; Prostaglandins

We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Diclofenac; Duodenum; Female; Gastric Mucosa; Gastrointestinal Diseases; Humans; Incidence; Intestinal Mucosa; Male; Misoprostol; Osteoarthritis; Time Factors

Patients who take nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk of upper gastrointestinal tract bleeding, which may be prevented with prophylactic prescription of misoprostol. Using data from the literature, we estimated rates of gastrointestinal tract bleeding in NSAID users, direct medical costs, years of life lost, and cost-effectiveness of a 1-year course of misoprostol in three clinical populations of NSAID users: all users, users aged 60 years or older, and users with rheumatoid arthritis. The incremental cost-effectiveness ratios for misoprostol as primary prevention were $667,400 per year of life saved for all NSAID users; $186,700 per year of life saved for users aged 60 years or older; and $95,600 per year of life saved for users with rheumatoid arthritis. Misoprostol as secondary prevention for those who continued to take NSAIDs despite having had an episode of gastrointestinal tract bleeding in the previous year was associated with incremental cost-effectiveness ratios less than $40,000 per year of life saved in all patient groups. We conclude that misoprostol is costly as primary prevention for NSAID-induced gastrointestinal tract bleeding in the groups examined but may be cost-effective as secondary prevention in patients with a proved history of gastrointestinal tract bleeding.

Topics: Aged; Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Costs and Cost Analysis; Decision Trees; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Life Expectancy; Middle Aged; Misoprostol; Patient Compliance; Probability; Sensitivity and Specificity; Stomach Ulcer

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Duodenal Ulcer; Humans; Misoprostol; Stomach Ulcer

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis, Rheumatoid; Female; Gastrointestinal Hemorrhage; Humans; Male; Misoprostol; Osteoarthritis; Peptic Ulcer

Topics: Alprostadil; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Therapy, Combination; Gastric Acidity Determination; Gastric Mucosa; Histamine H2 Antagonists; Humans; Intestinal Mucosa; Misoprostol; Peptic Ulcer; Sucralfate