Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumatoid arthritis but not psoriatic arthritis

Abstract

Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations.

Comparison between adalimumab introduction and methotrexate dose escalation in patients with inadequately controlled psoriatic arthritis (CONTROL): a randomised, open-label, two-part, phase 4 study

“…At 32 weeks, 41 (80%) of 51 adalimumab responders maintained MDA on adalimumab monotherapy following discontinuation of methotrexate, demonstrating limited value of adalimumab combination therapy with metho trexate in psoriatic arthritis, in contrast to rheumatoid arthritis. 32 This finding is in line with previous reports of adalimumab with or without methotrexate in psoriatic arthritis routine care, 23 and it could inform practitioner decisions surrounding reducing poly pharmacy in controlled disease. Similarly, ten (67%) of 15 methotrexate responders maintained MDA without further therapy adjustment, although interpretation of these results is limited by the small sample size.…”

Efficacy of secukinumab and adalimumab in patients with psoriatic arthritis and concomitant moderate‐to‐severe plaque psoriasis: results from EXCEED, a randomized, double‐blind head‐to‐head monotherapy study

“…The study evaluated an important current gap in our understanding by examining the initiation of biological monotherapy in patients with active PsA. Combination therapy with MTX and biologics has not been shown to be superior to biological treatment alone 22,23 and many patients discontinue MTX as primary or combination therapy because of poor tolerability and/or toxicity, or cannot receive MTX owing to liver abnormalities. 6,15 EXCEED is the first double-blind, randomized controlled head-to-head monotherapy study to compare secukinumab with adalimumab in patients with active PsA.…”

Is there still a place for methotrexate in severe psoriatic arthritis?

“…Changes in pain and function assessments showed a similar pattern. 33 Data regarding interleukin 17 inhibitors are similar. Ixekizumab demonstrated sustained efficacy in patients with PsA for up to 1 year of treatment, with or without concomitant MTX.…”

“…This was an observational study of patients with PsA ( N = 1424) who initiated adalimumab therapy during routine clinical care in Germany. 33 PsA patients who added MTX or stopped MTX showed similar modest improvements in mean DAS28 score at 6 months after the change, from 3.36 to 3.24 for MTX addition [mean difference, −0.12 (95% CI, −0.46 to 0.22); p = 0.47] and from 2.54 to 2.43 for MTX removal [mean difference, −0.10 (95% CI, −0.36 to 0.16); p = 0.44]. Changes in pain and function assessments showed a similar pattern.…”