fumarates and Arthritis--Psoriatic

Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries.. To assess the effects and safety of oral fumaric acid esters for psoriasis.. We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register.. Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis.. Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects.. We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not signific. Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.

Topics: Administration, Oral; Arthritis, Psoriatic; Dermatologic Agents; Fumarates; Humans; Methotrexate; Psoriasis; Randomized Controlled Trials as Topic; Severity of Illness Index

Severe cases of psoriasis and psoriasis arthritis require systemic treatment. Although a number of established drugs are in clinical use, there is a need for new compounds with an improved risk-benefit ratio with a major emphasis on long-term safety. Furthermore, patients with moderate psoriasis ask for systemic drugs to make therapy easier and to avoid excessive local treatments. This article aims to give a brief overview about new drugs or groups of compounds together with an evaluation of their present status in the treatment of psoriasis and their future role with particular respect to efficacy, tolerability, safety and usability.

Topics: Antibodies, Monoclonal; Anticarcinogenic Agents; Antigen-Presenting Cells; Arthritis, Psoriatic; Autoimmune Diseases; Dermatologic Agents; Fumarates; Humans; Immunosuppressive Agents; Immunotherapy; Keratolytic Agents; Platelet Aggregation Inhibitors; Psoriasis; Receptors, Cytoplasmic and Nuclear; Transcription Factors

To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis.. We searched Medline up to 1995, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings and contacting drug companies. All languages were included in the initial search.. All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. The main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include Acute Phase Reactants, Disability, Pain, Patient Global Assessment, Physician Global Assessment, Swollen joint count, Tender joint count and radiographic changes of joints in any trial of 1 year or longer [Tugwell 1993], and the change in pooled disease index. Only English trials were included in the review.. Data were independently extracted from the published reports by two of the reviewers. An independent blinded quality assessment was also performed.. Nineteen randomized trials were identified of which eleven were included in the quantitative analysis with data from 777 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.43 DI units, 95% CI 0. 28-0.59). There was insufficient data to examine toxicity.. Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.

Topics: Antirheumatic Agents; Arthritis, Psoriatic; Auranofin; Azathioprine; Dermatologic Agents; Etretinate; Fumarates; Humans; Immunosuppressive Agents; Methotrexate; Sulfasalazine

To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, efamol marine and methotrexate, in psoriatic arthritis.. We searched Medline up to February 2000, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings, contacting drug companies and referring to the Cochrane Clinical Trials Register. All languages were included in the initial search.. All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. Following a published a priori protocol, the main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include acute phase reactants, disability, pain, patient global assessment, physician global assessment, swollen joint count, tender joint count and radiographic changes of joints in any trial of one year or longer [Tugwell 1993], and the change in pooled disease index (DI). Only English trials were included in the review.. Data were independently extracted from the published reports by two of the reviewers (MC, GJ). An independent blinded quality assessment was also performed.. Twenty randomized trials were identified of which thirteen were included in the quantitative analysis with data from 1022 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was insufficient data to examine toxicity.. Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.

Topics: Antirheumatic Agents; Arthritis, Psoriatic; Auranofin; Azathioprine; Dermatologic Agents; Etretinate; Fumarates; Humans; Immunosuppressive Agents; Methotrexate; Sulfasalazine

Topics: Adult; Arthritis, Psoriatic; Double-Blind Method; Female; Fumarates; Humans; Male; Middle Aged

Topics: Adrenal Cortex Hormones; Anthralin; Arthritis, Psoriatic; Biological Products; Cyclosporine; Dermatologic Agents; Female; Fumarates; Humans; Male; Methotrexate; Phototherapy; Psoriasis; PUVA Therapy; Retinoids; Sex Factors