Does Adding Methotrexate to TNFis Provide a Clinical Benefit in Psoriatic Arthritis?

SAN DIEGO, CA—A post-hoc analysis of two trials found patients with active psoriatic arthritis treated with etanercept with or without methotrexate combination therapy had similar clinical and functional outcomes at 24 weeks of treatment, raising questions about the role of methotrexate, investigators concluded during the 2013 ACR/ARHP Annual Meeting.

“Previously, randomized controlled trials in psoriatic arthritis have allowed treatment with TNFi as monotherapy as well as co-medication with methotrexate; however, no trials have indicated a difference in response to TNFi in subgroups with and without concomitant methotrexate,” Bernard Combe, MD, PhD, of the Department of Rheumatology, Lapeyronie Hospital, Montpellier, France noted.

In addition, current psoriatic arthritis treatment guidelines do not provide clear recommendations on the use of TNFi as monotherapy or combined with methotrexate. “Recent real-life data found no additional benefit in response but a trend towards better drug survival in patients receiving TNFi and concomitant methotrexate,” study authors stated.

To evaluate clinical and functional outcomes in patients with active psoriatic arthritis receiving etanercept (25mg twice weekly or 50mg once weekly) with and without methotrexate, they pooled data from two clinical trials.

They summarized demographic and disease activity characteristics at baseline, Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology 20%, 50%, and 70% improvement (ACR20, 50, and 70) responses at 24 weeks, and change from baseline to Week 24 in Disease Activity Score based on 28-joint count using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Psoriasis Area and Severity Index (PASI) for patients in the etanercept and the combination arms across both studies.

At baseline, patients in the etanercept (n=322) and etanercept + methotrexate (n=152) arms had a mean age of 47.0 and 47.3 years and a weight of 84.7 kg and 87.1 kg, respectively; 38% and 42% were female. Duration of psoriasis was 18.4 and 17.5 years, respectively; duration of psoriatic arthritis, 8.2 and 9.0 years; DAS28-CRP, 4.7 and 4.7; HAQ-DI, 0.9 and 1.1; and PASI, 18.3 and 16.1. Other demographic and baseline disease characteristics were also similar for patients in the etanercept and etanercept + methotrexate arms.

Similar proportions of patients in both arms achieved PsARC (80.3% and 82.6%) and ACR20 responses (70.5% and 69.9%). Compared with the combination therapy arm, a higher proportion of patients in the etanercept arm achieved ACR50 (54.9% vs. 48.3%) and ACR70 (34.7% vs. 26.6%) responses. Change from baseline to Week 24 in the etanercept vs. combination therapy arms was DAS28-CRP (-1.9 vs. -1.8), HAQ-DI (-13.6 vs. -12(-0.5 vs. -0.6), and PASI.2), respectively.

“Further research is warranted to investigate the effect of concomitant methotrexate on responses and drug survival in patients with psoriatic arthritis starting their first tumor necrosis factor inhibitor (TNFi),” noted Dr. Combe.