Methotrexate boosts psoriatic arthritis remission rates for both adalimumab, infliximab
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Methotrexate increases the probability of remission with adalimumab or infliximab by 50% in patients with psoriatic arthritis, versus TNF-inhibitor monotherapy, according to data published in the Annals of the Rheumatic Diseases.
“Tumor necrosis factor inhibitors have become a cornerstone in the treatment of psoriatic arthritis,” Ulf Lindström, MD, PhD, of the University of Gothenburg, in Sweden, and colleagues wrote. “Despite this, no international consensus has been reached regarding the optimal use of TNFi in PsA. Thus, the current American College of Rheumatology guidelines recommend using TNFi as a first-line disease-modifying antirheumatic drug, and, in patients previously failing a conventional synthetic conventional synthetic DMARD, to switch to rather than to add a TNFi.”
“In contrast, the EULAR recommendations suggest using csDMARDs (methotrexate in particular) as the first-line DMARD and to then step up the treatment by adding, rather than switching to, a biological DMARD, such as a TNFi,” they added. “The discrepancy in international guidelines stems from the limited and conflicting data comparing the different treatment strategies.”
To compare treatment outcomes in patients with PsA who receive TNF-inhibitor and conventional, synthetic DMARD combination therapy, compared with TNF-inhibitor monotherapy, Lindström and colleagues conducted an observational study of data collected from 13 rheumatology registries in Europe.
Aggregated through the EuroSpA collaboration, the data included information on 15,332 adults with PsA starting a TNF inhibitor — adalimumab (Humira, AbbVie), certolizumab pegol (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) or infliximab (Remicade; Janssen, Johnson & Johnson) — during 2006 to 2017 from the Czech Republic, Denmark, Finland, Iceland, Italy, Norway, Portugal, Romania, Slovenia, Spain, Sweden, Switzerland and Turkey. Among these patients, 62% were receiving combination therapy, with the remaining 38% receiving monotherapy.
Lindström and colleagues compared 1-year TNF-inhibitor retention based on conventional, synthetic DMARD comedication status, specific to each country. They also calculated hazard ratios for TNF-inhibitor discontinuation based on comedication versus monotherapy status. Findings were adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated.
The researchers examined between-country heterogeneity using random-effect meta-analyses, with the combined results presented when heterogeneity was not significant. Secondary analyses, stratified according to TNF inhibitor subtype — either adalimumab, infliximab or etanercept — and restricted to methotrexate as combination therapy, were also performed.
According to the researchers, TNF-inhibitor retention varied across countries, with significant heterogeneity preventing a combined estimate. However, combination therapy was associated with better remission rates, with a pooled OR of 1.25 (95% CI, 1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR = 1.45; 95% CI, 1.23-1.72) and infliximab (OR = 1.55; 95% CI, 1.21-1.98), as well as improved retention with infliximab. Comedication demonstrated on impact for etanercept.
“We found improved clinical response rates when combining TNFi with a csDMARD,” Lindström and colleagues wrote. “More specifically, the rate of clinical remission for infliximab and adalimumab increased when combined with methotrexate, and the retention of infliximab was improved.
“For etanercept, the remission and retention rates did not differ between comedication and monotherapy — and were in line with the rates observed for adalimumab comedication,” they added. “Our findings support the prevailing strategy, in a situation of incomplete response, to continue methotrexate therapy when commencing treatment with infliximab or adalimumab, while for etanercept methotrexate may be discontinued.”
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