Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

Abstract

Background: Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse.

Objective: In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods).

Results: In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1-60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5-5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1-14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time.

Limitations: Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria.

Conclusions: These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.

Fig 1. PRISMA flow diagram according to [50] summarising study selection for clinical trials reporting safety (left) and efficacy (right) outcomes, respectively.

Search terms employed were: methotrexate [Title] AND (psoriasis [Title] OR arthritis [Title] OR Crohn’s [Title] OR ulcerative colitis [Title] OR ankylosing spondylitis [Title]) AND (trial [Title] OR Study [Title]) for safety studies and: Search: methotrexate [Title] AND psoriasis [Title] AND (trial [Title] OR Study [Title]) for efficacy studies.

Fig 2. Forest plot of efficacy of MTX in psoriasis as reported in the published clinical studies shown in Table 4.

The risk ratio shown refers to the PASI75 outcome reported at 12 or 16 weeks, respectively, assuming a random effects model (http://ije.oxfordjournals.org/content/39/2/421.full). One study (Dogra 2012) is listed twice because two distinct sub-cohorts were dosed differently (10 mg vs 25 mg), as described in the text.

Fig 3. Forest plot of all non treatment limiting adverse effects (Fig3a), as reported in the studies summarised in Table 2, as well as limiting AEs (Fig 3b).

All individual study data and forest plots for all individual AE’s are detailed in the Supplement. Underlined studies were conducted for psoriasis as indication.