levoleucovorin and Psoriasis

Methotrexate (MTX) is an effective treatment option for patients with moderate-to-severe psoriasis. As psoriasis is an incurable disease, the goal of the MTX treatment is to suppress psoriasis, achieving long-term remissions with minimal treatment-related adverse events (AEs).. Supplementation with folate - either folic acid (FA) or folinic acid - may reduce the side effects of MTX therapy. There are no consistent, evidence-based guidelines for folate supplementation in this clinical setting. We present data concerning the impact of folic supplementation on the safety and efficacy of MTX therapy for psoriasis. An extensive search (1960 - March 2014) identified few studies addressing with just one randomized controlled trial (RCT) and some case series. This meager yield underlines the need for further studies, especially RCTs, in this group of patients.. FA may be effective in diminishing the severity of AEs in patients with psoriasis treated with MTX and should be recommended. Supplementation with too high doses of FA may influence the efficacy of treatment.

Topics: Antirheumatic Agents; Dose-Response Relationship, Drug; Folic Acid; Humans; Leucovorin; Methotrexate; Psoriasis; Severity of Illness Index; Vitamin B Complex

Methotrexate is a folic acid antagonist widely used for the treatment of inflammatory disorders for more than 50 years. Methotrexate is a standard systemic therapy for severe psoriasis and rheumatoid arthritis. Folic acid supplementation has been advocated to limit the toxicity of methotrexate on blood cells, gastrointestinal tract and liver. However, there is still controversy regarding the usefulness of folic acid supplementation.. We sought to assess the evidence for the efficacy of folic acid supplementation in patients treated with methotrexate for inflammatory diseases. We also investigated whether folic acid supplementation may decrease the efficacy of methotrexate.. Cochrane and MEDLINE databases were systematically searched. Randomized controlled trials in patients treated with methotrexate for rheumatoid arthritis or psoriasis with or without arthritis were included. Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent researchers. We selected double-blind randomized placebo-controlled trials. Analysis was performed for each subgroup of side-effects: gastrointestinal, mucocutaneous, haematological and hepatic.. Six randomized controlled trials met the inclusion criteria, with a total sample of 648 patients. There were 257 patients in the placebo group, 198 patients treated with folic acid, and 193 patients treated with folinic acid. The statistical analysis showed a significant reduction of 35.8% of hepatic side-effects induced by methotrexate for patients with supplementation with folic or folinic acid (95% confidence interval -0.467 to -0.248). There was no statistical difference for mucocutaneous and gastrointestinal side-effects although there was a trend in favour of supplementation. The effect of supplementation on haematological side-effects could not be assessed accurately due to a low incidence of these events in the population studied. We were unable to analyse the effect of supplementation on the effectiveness of methotrexate, as markers of activity used in each study were not comparable.. Supplementation with folic acid is an effective measure to reduce hepatic adverse effects associated with methotrexate treatment. There is no difference between folinic acid and folic acid, but the lower cost of the latter promotes its use.

Topics: Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Drug Eruptions; Folic Acid; Gastrointestinal Diseases; Hematologic Diseases; Humans; Immunosuppressive Agents; Leucovorin; Liver Diseases; Methotrexate; Psoriasis; Randomized Controlled Trials as Topic

Methotrexate is a folate antagonist that is a well-established therapy for autoimmune and inflammatory conditions. In some patients, methotrexate is associated with significant side effects and toxicity. Folate supplementation is often used to ameliorate methotrexate-associated side effects and toxicities. We sought to demonstrate that folate supplementation during methotrexate therapy reduces both toxicity and side effects without compromising efficacy. A MEDLINE search of the search terms "methotrexate," "folic acid," "folinic acid," and "leucovorin" was performed and literature relevant to the use of folates as a supplement to methotrexate was reviewed. According to studies reviewed, the use of folate supplements in patients treated with methotrexate reduces the incidence of hepatotoxicity and gastrointestinal intolerance without impairing the efficacy of methotrexate. Both folic acid and folinic acid are equally effective; however, folic acid is more cost effective. It must be noted that there are relatively few studies that have addressed folate supplementation with the use of methotrexate for the treatment of psoriasis. After examining the available data from the literature and drawing from clinical experience, we advise folate supplementation for every patient who receives methotrexate.

Topics: Drug Therapy, Combination; Folic Acid; Gastrointestinal Tract; Hematinics; Humans; Immunosuppressive Agents; Leucovorin; Methotrexate; Psoriasis

Methotrexate (MTX) has become one of the most widely prescribed second-line agents world-wide for rheumatoid arthritis (RA). Studies have established efficacy in populations which have failed other second-line agents. Although MTX must be considered as a potential hepatotoxin, studies have shown that liver histologic changes can be predicted by monitoring of serum albumin and AST at four to eight week intervals. MTX pulmonary toxicity appears to be more common than liver disease. It most often presents with a subacute course with dry cough and dyspnea with or without fever. Clinicians must be aware of this presentation and withhold the drug when these symptoms appear. MTX may also cause mild renal impairment when used with NSAIDs. This effect has been observed with higher mean weekly doses in the 15 to 20 mg range, but not with a starting dose of 7.5 mg. Although MTX may exhibit a variety of effects in in vitro systems its mechanism of action in patients with RA has not yet been determined.

Topics: Antidotes; Antirheumatic Agents; Arthritis, Rheumatoid; Dermatologic Agents; Drug Therapy, Combination; Folic Acid; Hematinics; Humans; Kidney; Leucovorin; Liver; Lung; Methotrexate; Psoriasis

Topics: Abnormalities, Drug-Induced; Bone Marrow; Chemical and Drug Induced Liver Injury; Female; Hematologic Diseases; Humans; Kidney Diseases; Leucovorin; Liver; Methotrexate; Pregnancy; Psoriasis; Skin

Studies on thirty-six psoriatics revealed no differences in acute liver toxicity of four different intermittent dosage schedules of methotrexate with or without addition of leucovorin, as judged by daily determinations of SGOT for one week. Three patients with psoriatic erythroderma receiving high-dosage methotrexate (100 mg i.v.) with leucovorin rescue responded extremely well to treatment and did not distinguish themselves from the other patients with regard to acute liver toxicity.

Topics: Administration, Oral; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Injections, Intramuscular; Injections, Intravenous; Leucovorin; Methotrexate; Psoriasis

Even today methotrexate (MTX) remains the backbone of psoriasis management in dermatological practice. The widespread usage as well as over the counter availability of drug in India has led to frequent incidents of overdosing, resulting in toxicity. However, there is a lack of large size, comprehensive study in literature emphasizing upon reasons behind drug toxicity, clinical manifestations, and various management aspects. The present study aims to evaluate risk factors, clinical features, and suggest best management protocol based upon our experience in the management of MTX toxicity. A multicentric, retrospective study was conducted including all cases of psoriasis who were treated for MTX toxicity in the last 5 years. Complete information including demographic details, drug history, detailed clinical evaluation, laboratory parameters, management protocol, and outcome were studied and analyzed. A total of 21 patients of psoriasis with MTX toxicity were included, of which 20 had mucocutaneous ulcerations and hematological abnormalities were found in 76% patients. All cases were treated with folinic acid and 85% patients recovered within 7-14 days. Three out of 21 patients succumbed to their illness despite the best possible treatment. Overdosing was found to be the most common cause (66%) of drug toxicity, either inadvertent or due to self-medication. Patients must be counseled regarding course of the disease, drug regimen, and dreaded side effects prior to initiating the drug. In case the symptoms of toxicity appear, a prompt medical advice must be sought.

Topics: Drug-Related Side Effects and Adverse Reactions; Humans; India; Leucovorin; Methotrexate; Psoriasis; Retrospective Studies

Topics: Adult; Antidotes; Drug-Related Side Effects and Adverse Reactions; Early Diagnosis; Hemorrhage; Humans; Immunosuppressive Agents; Leucovorin; Male; Methotrexate; Mucous Membrane; Pancytopenia; Psoriasis; Skin; Treatment Outcome; Withholding Treatment

Topics: Buffers; Dermatologic Agents; Drug Overdose; Fluid Therapy; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Psoriasis; Skin Ulcer; Sodium Bicarbonate; Treatment Outcome

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.

Topics: Acute Kidney Injury; Adult; Azithromycin; Biopsy; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Leucovorin; Male; Methotrexate; Mucositis; Necrosis; Pancytopenia; Plasma; Psoriasis; Recombinant Proteins; Self Medication; Skin Ulcer; Trimethoprim, Sulfamethoxazole Drug Combination

To determine which risk factors are associated with serious pancytopenia associated with low dose methotrexate (MTX) therapy.. All Ottawa area rheumatologists, hematologists and dermatologists were surveyed to obtain cases of pancytopenia associated with low dose MTX therapy between 1981 and 1991. Pancytopenia was defined as white blood cells < 3.5 x 10(9)/l and platelets < 140 x 10(9)/l and hemoglobin < 100 g/l. A case control method was used to evaluate risk factors.. Fifteen cases of pancytopenia were identified from returned questionnaires (93% response rate) and from reviewing the medical records of 2 major teaching hospitals. All patients were hospitalized, had MTX therapy discontinued and were treated: 12 patients received transfusions, 8 leucovorin therapy, and 4 folic acid. Two patients died, only 1 directly due to MTX therapy. Identified risk factors were (1) elevated BUN or creatinine levels, (2) increasing mean corpuscular volume values, (3) increased age and (4) concomitant trimethoprim-sulfamethoxazole therapy.. Pancytopenia associated with low dose MTX therapy is a life threatening adverse effect often associated with known risk factors. A change in monitoring guidelines and patient education are suggested as means of risk reduction.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arthritis, Psoriatic; Arthritis, Rheumatoid; Blood Urea Nitrogen; Canada; Creatinine; Dose-Response Relationship, Drug; Female; Folic Acid; Health Surveys; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Pancytopenia; Psoriasis; Risk Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Many combinations of methotrexate and folic or folinic acid have been used to limit the side effects of methotrexate therapy in psoriasis or psoriatic arthropathy. Methotrexate inhibits the enzyme dihydrofolate reductase and prevents the formation of DNA and RNA. Folinic acid, the 5-formyl derivative of tetrahydrofolic acid, is the active form of folic acid. We have confirmed in 5 patients that continuous administration of folinic acid with weekly oral methotrexate prevents improvement of psoriasis. When folinic acid was ceased on the day of methotrexate in these patients their psoriasis improved. Five other patients with previous sensitivity to methotrexate, forcing cessation of therapy, were given weekly oral methotrexate and folinic acid every day except the day of methotrexate. Marked improvement of psoriasis or arthropathy occurred in each case without side effects. This method precisely limits the exposure to methotrexate, allowing a therapeutic effect without complication even in those patients who exhibit methotrexate sensitivity.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Humans; Leucovorin; Male; Methotrexate; Psoriasis

Topics: Adult; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Psoriasis

Topics: Drug Combinations; Humans; Leucovorin; Methotrexate; Psoriasis

Topics: Anemia, Hypochromic; Chemical and Drug Induced Liver Injury; Chromosome Aberrations; Chromosome Disorders; Drug Eruptions; Folic Acid Antagonists; Headache; Humans; Leucovorin; Methotrexate; Mouth Diseases; Mouth Mucosa; Nausea; Psoriasis; Vertigo

Topics: Humans; Leucovorin; Methotrexate; Psoriasis

Topics: Aged; Humans; Leucovorin; Methotrexate; Middle Aged; Psoriasis

Topics: Adult; Anemia, Aplastic; Blood Cell Count; Chemical and Drug Induced Liver Injury; Hepatomegaly; Humans; Leucovorin; Liver; Liver Function Tests; Male; Methotrexate; Psoriasis; Splenomegaly; Time Factors