Initiation of biologic therapy early in the course of psoriatic arthritis doubled the remission rate at week 22 in a randomized trial.
In patients who had previously received neither methotrexate nor a biologic agent, the remission rate among those who were given monthly subcutaneous golimumab (Simponi) plus methotrexate was 81% compared with 42% for those given methotrexate alone (P=0.004), according to Dominique Baeten, MD, PhD, of the University of Amsterdam, and colleagues. Remission was defined as a Disease Activity Score below 1.6.
And statistically significant differences between the two treatment arms were already apparent by week 8, when remission had been achieved by 73% of the combination golimumab group compared with 42% of the methotrexate monotherapy group, the researchers reported online in Annals of the Rheumatic Diseases.
In contrast to rheumatoid arthritis, where early, aggressive treat-to-target strategies have become standard of care, treatment of psoriatic arthritis today typically relies on the older step-up model, starting with nonsteroidal anti-inflammatory drugs (NSAIDs) and nonbiologic disease-modifying antirheumatic drugs, particularly methotrexate, despite the fact that the efficacy of methotrexate for this indication remains uncertain.
“Methotrexate reflects current standard of care despite the fact that previous trials of methotrexate in psoriatic arthritis failed to unequivocally establish efficacy,” the researchers stated.
A previous open-label study suggested that patients with early psoriatic arthritis could have greater improvements with a different tumor necrosis factor inhibitor, infliximab (Remicade) plus methotrexate, than with methotrexate alone. That prompted Baeten and colleagues to initiate their double-blind trial with 50 patients from three centers in the Netherlands from 2013 to 2017.
Golimumab was administered in dosages of 50 mg once monthly, and in both groups, oral methotrexate was started in dosages of 15 mg/week and titrated up to 25 mg/week over an 8-week period. Previous studies that failed to show efficacy for methotrexate monotherapy had not used this optimal dosage titration, the researchers noted. Patients were permitted to use concurrent NSAIDs and corticosteroids in stable dosages below 10 mg/day.
Participants’ mean age was 47, and mean time since diagnosis was 0.5 years. The majority of patients had polyarticular disease, with median swollen and tender joint counts of five and ten, respectively.
In 20 of the patients, the Psoriasis Area and Severity Index (PASI) was 2.5 or more at baseline, and dactylitis and enthesitis were present in 17 and 11, respectively.
Improvements on a number of secondary endpoints also were greater in the golimumab group. For instance, minimal disease activity was reached by 81% versus 29% (P<0.001). This endpoint required tender and swollen joint counts of one or less, PASI of 1 or less, patient pain score of 15 or less, global disease activity scores of 20 or lower, health assessment questionnaire scores of 0.5 or less, and one or fewer tender entheseal points.
In addition, improvements on standard American College of Rheumatology criteria (20%, 50%, and 70% reduction in symptom scores) were observed more often in the golimumab group than in the placebo group:
- ACR20: 85% vs 58% (P=0.039)
- ACR50: 81% vs 33% (P=0.001)
- ACR70: 58% vs 13% (P=0.001)
For patient-reported outcomes, scores again favored golimumab treatment, with patient pain scores at week 22 being 6 versus 34 (P=0.001) and patient global scores being 9 versus 31 (P=0.038).
However, significant differences were not seen for function or quality of life, with scores on the Health Assessment Questionnaire of 0 versus 0.25 (P=0.403) and on the Dermatology Life Quality Index of 1 versus 0 (P=0.072). The lack of effect on these aspects of disease needs further exploration, the researchers stated.
The most common adverse event was nausea, which was seen at similar rates in the two groups and led to temporary stopping or dose lowering of methotrexate in 18 patients.
“Taken together with the good tolerability and absence of novel safety signals, these results … suggest the value of early intervention in psoriatic arthritis rather than the classical step-up approach,” they concluded.
Limitations of the study were its small size and brief duration.
The study was supported by an unrestricted grant from Merck Sharp & Dohme.
The authors reported financial relationships with Merck Sharp & Dohme, UCB, AbbVie, Novartis, Janssen, Eli Lilly, Bristol-Myers Squibb, Pfizer Celgene, Mundipharma, Roche, and Sanofi.