For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.
In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.
Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.
Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).
Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”
They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.
The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.
Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.
SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.