March 13, 2016
MAUI, HAWAII – The effectiveness of methotrexate in psoriatic arthritis is a matter of debate, but Dr. Arthur Kavanaugh is a believer based in part upon a recent subanalysis of the TICOPA study.
Moreover, his new 5-year follow-up analysis from the GO-REVEAL study of golimumab (Simponi) with or without concomitant methotrexate suggests that methotrexate plus the tumor necrosis factor inhibitor provided synergistic efficacy, he said at the 2016 Rheumatology Winter Clinical Symposium.
The 5-year analysis doesn’t provide definitive proof of synergistic benefit because it wasn’t designed or powered with that endpoint in mind (Arthritis Care Res. 2016;68:267–74). No randomized trial completed to date has been. But the first-ever trial set up to test the synergistic efficacy hypothesis is underway. It’s a 52-week, double-blind, multicenter, randomized trial of etanercept (Enbrel) and methotrexate versus either alone in combination with placebo. And while the Amgen-sponsored study won’t be completed until 2018, Dr. Kavanaugh is ready to predict the outcome based in part upon the message contained in his GO-REVEAL findings.
“I’m placing my bet down now that there will be synergy for the X-ray outcome of change in SHS [Sharp/van der Heijde Score] for sure, and maybe for clinical efficacy as well, both joints and skin,” declared Dr. Kavanaugh, the conference director and professor of medicine at the University of California, San Diego.
He pointed to a new subanalysis of the Tight Control of Psoriatic Arthritis (TICOPA) study reported by rheumatologists at the University of Leeds (England) as evidence that methotrexate is effective in psoriatic arthritis. Of the 188 patients in the tight control arm who received methotrexate in the first 12 weeks of the trial, 41% had an ACR 20 response, meaning a 20% improvement in disease signs and symptoms at 12 weeks. A total of 19% had an ACR 50 response. And 27% had at least a 75% improvement in Psoriasis Area and Severity Index, or PASI 75. A 63% reduction in the proportion of patients with dactylitis and a 26% decrease in the proportion of patients with enthesitis was observed in the early methotrexate group. There was a suggestion of a dose-response effect, with better outcomes seen in the 108 participants who received a mean dose greater than 15 mg/week (J Rheumatol. 2016 Feb;43:356-61).
This is a more impressive result than earlier reported from the Methotrexate In Psoriatic Arthritis (MIPA) trial, where the ACR 20 response rate was only 34% (Rheumatology [Oxford]. 2012;51:1368-77). That may well be because methotrexate was given at only 15 mg/week in MIPA, in Dr. Kavanaugh’s view.
“I think methotrexate can work for the peripheral arthritis. This TICOPA analysis gives us a sense of the extent of the improvement, and also the extent of improvement in the skin,” the rheumatologist commented.
Turning to the week 256 results of GO-REVEAL, he said there was no difference in clinical response between psoriatic arthritis patients on golimumab alone or golimumab plus methotrexate at baseline. But among patients who were doing well clinically, with an assessment of minimal disease activity (MDA) on three or more consecutive clinic visits, only those on golimumab plus methotrexate at baseline showed radiologic improvement. The 57 patients on combination therapy who achieved MDA on at least three consecutive visits showed a mean 1.29-point improvement in SHS; the 48 rated as having MDA on four or more consecutive occasions similarly had a mean 1.24-point improvement.
In contrast, the 59 participants who achieved MDA on three or more consecutive visits but were on golimumab without methotrexate at baseline had a 0.25-point increase in SHS, and the 47 who had MDA on at least four consecutive visits had a 0.38-point SHS bump.
Dr. Kavanaugh reported having financial relationships with roughly a dozen pharmaceutical companies