Methotrexate and histologic hepatic abnormalities: A meta-analysis

Whiting-O'Keefe, Quinn E.; Fye, Kenneth H.; Sack, K

doi:10.1016/s0002-9343(05)80060-9

Cited by 295 publications

(134 citation statements)

References 28 publications

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“…Even MTX, the most widely used DMARD in RA and PsA, has more evidence of hepatic toxicity and less evidence of efficacy in PsA than in RA (10,37,38). Sulfasalazine has shown marginal efficacy in PsA, based on a composite end point (the PsARC), but the improvement in the individual components did not reach statistical significance, and studies with sulfasalazine have had high rates of premature discontinuation (29,39).…”

Section: Discussionmentioning

confidence: 99%

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double‐blind, randomized, placebo‐controlled trial

Mease

Gladman

Ritchlin

et al. 2005

Arthritis & Rheumatism

837

629

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Objective. Adalimumab, a fully human, antitumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA).Methods. Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area.Results. At week 12, 58% of the adalimumabtreated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was ؊0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumabtreated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and welltolerated.Conclusion. Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis occurring in individuals with psoriasis. Psoriasis occurs in 2-3% of the US population (1). The reported range of prevalence of PsA in patients with psoriasis is 6-39%, depending on the population studied

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Section: Discussionmentioning

confidence: 99%

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double‐blind, randomized, placebo‐controlled trial

Mease

Gladman

Ritchlin

et al. 2005

Arthritis & Rheumatism

837

629

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“…Because of the high placebo response rate in patients with PsA (14), data from uncontrolled trials may be misleading. In addition, discontinuation rates due to lack of response and adverse events are typically high for conventional systemic therapies (38), and longterm safety is a concern (39,40). Two biologic agents, etanercept and infliximab, have recently been shown to be effective in the treatment of PsA, and these agents along with alefacept also reduce psoriasis symptoms (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the data suggest that liver effects are comparable in these 2 patient populations, with transaminase elevations reported as an adverse event for 14.8% of leflunomidetreated RA patients in a controlled clinical trial (22) compared with 12.5% of leflunomide-treated PsA patients in the current study. This is a potentially important observation given the increased hepatotoxicity of MTX in patients with PsA relative to patients with RA (39). Although long-term data from patients with PsA are not yet available, studies in RA indicate that the efficacy and safety of leflunomide are maintained for at least 5 years (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational, double‐blind, randomized, placebo‐controlled clinical trial

Kaltwasser

Nash

Gladman

et al. 2004

Arthritis & Rheumatism

374

194

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Objective. Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis.Methods. One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed.Results Conclusion. Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.

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“…Non-alcoholic steatohepatitis and obesity have shown no greater risk for liver toxicity but in cases induced by methotrexate and tamoxifen (43)(44)(45)(46). Multiple studies have shown an increased risk of elevated ALT in patients coinfected with HIV and HBV or HCV as compared to HIV infection alone during antiretroviral therapy, but telling hepatotoxicity from an underlying liver disease exacerbation is sometimes challenging (41)(42)(43).…”

Section: Special Situations In Causality Assessmentmentioning

confidence: 99%