A randomized, double‐blind, placebo‐controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Abstract

BackgroundEtanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis.ObjectivesTo evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy.MethodsPatients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24.ResultsIn total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm.ConclusionsCombination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.

Which Antipsoriatic Drug Has the Fastest Onset of Action?—Systematic Review on the Rapidity of the Onset of Action

“…During treatment with low-dose etanercept (2 Â 25 mg or 1 Â 50 mg per week), a duration of 9.5 weeks was necessary to achieve a PASI 75 response in 25% of the patients (2 study arms, n ¼ 153) (Gottlieb et al, 2003;van de Kerkhof et al, 2008). On using a dosage of 2 Â 50 mg of etanercept (5 study arms, n ¼ 1.177) a period of 6.6 weeks was required to reach this outcome (Tyring et al, 2007;Griffiths et al, 2010;Gottlieb et al, 2011Gottlieb et al, , 2012Strober et al, 2011). A treatment with infliximab (7 study arms, n ¼ 1.710) showed PASI 75 response in 25% of patients within 3.5 weeks (Reich et al, 2005;Menter et al, 2007;Torii and Nakagawa, 2010;Barker et al, 2011;Noda et al, 2012;Yang et al, 2012).…”

Combining biologics with methotrexate in psoriasis: a systematic review

“…same in psoriasis because of their inherent higher risk of non-alcoholic fatty liver disease 11,12 . In view of the results in Table 1, a MTX dose ranging from 5-15 mg/week may be considered for improving efficacy and drug survival while limiting the risk of hepatotoxicity 6,13,14 We conclude that the available evidence on combination treatment of biologics and MTX in psoriasis is currently not sufficient to propose an amendment of the current treatment guidelines. However, our findings do support the initiation of adequately powered RCTs to compare biologic monotherapy versus MTX combination therapy in psoriasis.…”

Effectiveness End Points in Real-World Studies on Biological Therapies in Psoriasis: Systematic Review with Focus on Drug Survival

“…In particular, non-naive patients to biological therapies seem to report a reduced effectiveness – and consequently a shorter drug survival – of subsequent biological therapies [25]. Similarly, concomitant use of methotrexate and biological treatment has been associated with an improved efficacy, since it decreases the formation of antidrug antibody [88]. Since high heterogeneity exists across studies for the reported factors, future studies with a meta-analytic approach should carefully explore this heterogeneity and variability through subgroup and sensitivity analyses.…”