mobic and Arthritis--Juvenile

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain.. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries.. Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator.. Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables.. We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/15. We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Arthritis, Rheumatoid; Aspirin; Celecoxib; Child; Child, Preschool; Chronic Disease; Chronic Pain; Fenoprofen; Humans; Ibuprofen; Lactones; Meloxicam; Methoxsalen; Naproxen; Randomized Controlled Trials as Topic; Sulfones; Thiazines; Thiazoles

Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.

Topics: Antibodies, Blocking; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Juvenile; Child; Child, Preschool; Humans; Immunologic Factors; Infliximab; Isoxazoles; Leflunomide; Meloxicam; Methotrexate; Naproxen; Rheumatology; Thiazines; Thiazoles

To compare the safety and efficacy of rofecoxib* to naproxen for the treatment of juvenile rheumatoid arthritis (JRA).. This was a 12-week, multicenter, randomized, double-blind, double-dummy, active comparator-controlled, non-inferiority study with a prespecified 52-week open-label active comparator-controlled extension. Children (ages 2-11 yrs) and adolescents (ages 12-17 yrs) received lower-dose (LD)-rofecoxib [0.3 mg/kg/day up to 12.5 mg/day (base study only)]; or higher-dose (HD)-rofecoxib (0.6 mg/kg/day up to 25 mg/day) or naproxen 15 mg/kg/day as oral suspensions. Adolescents received daily rofecoxib (LD) 12.5 (base study only) or (HD) 25 mg, or naproxen 15 mg/kg/day (maximum 1,000 mg/day) as tablets. The primary endpoint was the time-weighted average proportion of patients meeting the American College of Rheumatology Pediatric-30 (ACR Pedi 30) response criteria. A prespecified bound for the 95% confidence interval for the ratio of the percentage of ACR Pedi 30 responders was used to assess non-inferiority of treatment response between groups. Safety was assessed throughout the study.. A total of 310 patients ages 2-17 years (181 (3/4) age 11) were randomized to receive LD-rofecoxib (N=109), HD-rofecoxib (N=100), or naproxen (N=101). The ACR Pedi 30 response rates following 12 weeks of treatment were 46.2%, 54.5%, and 55.1%, respectively. The relative rates of response compared to naproxen were 0.81 (95% CI 0.61, 1.07) and 0.98 (95% CI 0.76, 1.26) for LD- and HD-rofecoxib, respectively. Both rofecoxib doses were not inferior to naproxen. Patients (N=227) entering the extension received HD-rofecoxib or naproxen with efficacy maintained during the extension. All treatments were generally well tolerated throughout the study.. Daily treatment of JRA patients with rofecoxib up to 12.5 or 25 mg was well tolerated, providing sustained clinical effectiveness comparable to naproxen 15 mg/kg. *On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.

Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Lactones; Longitudinal Studies; Male; Meloxicam; Naproxen; Sulfones; Thiazines; Thiazoles; Treatment Outcome

In an international, multicenter, double-blind, randomized clinical trial we evaluated the short-term (3 months) and long-term (12 months) efficacy and safety of 2 different doses of meloxicam oral suspension compared with the efficacy and safety of naproxen oral suspension in children with oligoarticular-course (oligo-course) or polyarticular-course (poly-course) juvenile idiopathic arthritis (JIA).. Children ages 2-16 years who had active oligo-course or poly-course JIA and who required therapy with a nonsteroidal antiinflammatory drug were eligible for this trial. Patients were randomly allocated to receive therapy with meloxicam oral suspension, 0.125 mg/kg body weight in a single daily dose; meloxicam oral suspension, 0.25 mg/kg body weight in a single daily dose; or naproxen, 10 mg/kg body weight in 2 daily doses. The trial drugs were administered in a double-blind, double-dummy design for up to 12 months. Response rates were determined according to the American College of Rheumatology pediatric 30% improvement criteria (ACR pediatric 30). Safety parameters were assessed by evaluating the frequency of adverse events in the 3 groups.. Of 232 patients enrolled, 225 received treatment, 6 were not eligible for randomization, and 1 randomized patient was not treated. One hundred eighty-two patients (81%) completed the 12-month treatment period. Response rates according to the ACR pediatric 30 criteria improved from month 3 to month 12, as follows: from 63% to 77% in the meloxicam 0.125 mg/kg group, from 58% to 76% in the meloxicam 0.25 mg/kg group, and from 64% to 74% in the naproxen group. No statistically significant differences in response rates were observed between the groups. There were no differences in the frequency of adverse events or abnormal laboratory values between the 3 groups.. The short- and long-term safety and efficacy of meloxicam oral suspension appear to be comparable with the safety and efficacy of naproxen oral suspension in the treatment of oligo-course and poly-course JIA. The once-daily administration of meloxicam oral suspension might represent an improvement in the treatment of JIA.

Topics: Administration, Oral; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child; Child, Preschool; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Humans; Male; Meloxicam; Naproxen; Thiazines; Thiazoles; Treatment Outcome

The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25-mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variation for geometric mean [gCV]) C(max), AUC(0- infinity ), apparent clearance, apparent volume of distribution, and elimination half-life values were 1.24 microg/mL (47% gCV), 25.6 microg x h/mL (81% gCV), 0.17 mL/min/kg (83% gCV), 0.19 L/kg (63% gCV), and 13.4 hours (54% gCV) in the younger group and 1.89 microg/mL (25% gCV), 35.8 microg x h/mL (21% gCV), 0.12 mL/min/kg (23% gCV), 0.13 L/kg (22% gCV), and 12.7 hours (21% gCV) for the older group, respectively. Area under the curve, volume of distribution, and clearance tended to be higher in the younger group, whereas elimination half-lives were similar. A post hoc comparison to pharmacokinetic data in adults revealed no relevant differences. Thus, a common body weight-normalized dose is considered appropriate for children older than 2 years.

Topics: Administration, Oral; Adolescent; Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Arthritis, Juvenile; Child; Child, Preschool; Cyclooxygenase Inhibitors; Female; Germany; Half-Life; Humans; Male; Meloxicam; Mexico; Thiazines; Thiazoles

Use of meloxicam as a selective COX-2 inhibitor for treatment of adult rheumatic diseases decreases the frequency of gastrointestinal (GI) side effects in comparison with nonselective COX inhibitors. Up to 50% of children with juvenile rheumatoid arthritis (JRA) also develop GI side effects through nonselective COX inhibitors. In this 12 week Phase I/II study, with an additional open extension lasting up to 52 weeks, the safety, efficacy, and pharmacokinetics of meloxicam in JRA were investigated.. Meloxicam suspension 0.25 mg/kg once daily was given to 36 patients with JRA who required a nonsteroidal antiinflammatory drug. Safety evaluation and periodic measurement of efficacy were carried out using the Pediatric Rheumatology International Trials Organisation (PRINTO) criteria. Eighteen patients underwent pharmacokinetic (PK) evaluation.. Thirty-one patients completed the study. Four were dropped due to administrative reasons. One patient, who found the drug ineffective, discontinued participation. A response was seen according to PRINTO outcome criteria in 44% of the patients at Week 4, 62% at Week 12, and 74% at Week 52. Drug related adverse events were observed in 5 patients. PK evaluation showed that the maximum plasma concentration Cmax of -34% and AUC(0-infinity) of -28% tended to be lower in younger children (2-6 years) versus older children. Plasma elimination half-life (13 h) was similar in all patients.. Meloxicam suspension 0.25 mg/kg once daily seems to be effective and safe for treating active JRA over a period of 52 weeks.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child; Child, Preschool; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Female; Humans; Isoenzymes; Male; Meloxicam; Membrane Proteins; Patient Satisfaction; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles; Treatment Outcome

To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS).. The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI).. The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change.. The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Juvenile; Blood Sedimentation; Child; Child, Preschool; Cross-Sectional Studies; Disability Evaluation; Humans; Joints; Meloxicam; Methotrexate; Naproxen; Outcome Assessment, Health Care; Prognosis; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome