Adding methotrexate (MTX) to etanercept (ETN) did not result in significantly greater arthritis symptom improvement in patients with psoriatic arhtirits (PsA), according to a study published in The Journal of Rheumatology. This may be clinically important in the subset of PsA patients who have a history of MTX intolerance or contraindication to MTX therapy.
“In systematic reviews, anti-TNF agents combined with MTX in PsA were not found to provide greater improvement in clinical symptoms than anti-TNF monotherapy, but combination therapy appeared to be involved in prolonging anti-TNF continuation and decreasing side effects,” the authors noted.
Possible differences in TNF drug survival with the addition of MTX to anti-TNF monotherapy prompted researchers to analyze if there were corresponding improvements in clinical PsA symptoms or psoriasis skin manifestations.
Bernard Combe, MD, of the Lapeyronie Hospital and Montpellier University, and colleagues analyzed the results of 2 clinical trials, the Psoriasis Randomized Etanercept Study in Subjects with Psoriatic Arthritis (PRESTA, ClinicalTrials.gov Identifier: NCT00245960) and the Double-Blind, Randomized, Placebo-Controlled Study of Etanercept in the Treatment of Psoriatic Arthritis and Psoriasis (ClinicalTrials.gov Identifier NCT00317499).
Though prior randomized clinical trials had assessed the efficacy and safety of ETN when added to MTX treatment for PsA, none have directly evaluated outcomes of anti-tumor necrosis factor (TNF) monotherapy as compared to anti-TNF and MTX combination therapy.
“Because the design and patient populations of [these two] clinical trials were relatively similar, posthoc analyses were conducted using pooled data from the trials to evaluate potential differences in clinical and functional outcomes in patients with PsA who received ETN with and without MTX,” the authors reasoned.
Combined analysis included 322 study participants in the ETN monotherapy intent-to-treat (ITT) group and 152 study participants in the ETN plus MTX combination ITT group. In both treatment groups demographic and clinical disease characteristics at baseline were similar.
In terms of changes in skin involvement, Psoriasis Area Severity Index (PASI) improvement of 75% (PASI75) scores were also comparable in both analysis groups.
After 24 weeks of treatment, PsA Response Criteria (PsARC) was achieved by 80.3% (95% confidence interval [CI] 75.8–84.8) and 82.6% (CI 76.5–88.8) of patients in the ETN monotherapy and ETN-MTX combination therapy groups, respectively. American College of Rheumatology improvements of 20% (ACR20) scores were 70% in both ITT groups.
Proportions of patients in the ETN monotherapy group achieving ACR50 were numerically higher as compared with the combination therapy group (54.9%, [CI 49.1–60.6] vs 48.3%, [CI 40.1–56.4]). The same trend persisted for proportions of study participants achieving ACR 70 (34.7% [CI 29.2–40.2] vs 26.6%, [CI 19.3–33.8]).
Summary and Clinical Applicability
Similar proportions of patients with PsA attained improvements in ACR20 scores among those receiving ETN monotherapy as compared with combination therapy of ETN and MTX. It should be noted that the 20-week analysis time period defined in this analysis may not be long enough to assess effects of differential long-term treatment.
Limitations and Disclosures
The studies analyzed were not designed or powered to detect differences in clinical outcomes between ETN monotherapy and ETN-MTX combination therapy.
Combe B, Behrens F, Mchugh N, et al. Comparison of Etanercept Monotherapy and Combination Therapy with Methotrexate in Psoriatic Arthritis: Results from 2 Clinical Trials. J Rheumatol. 2016; Published online before print. May 1, 2016; doi:10.3899/jrheum.151290.