Background/Purpose: Methotrexate is frequently administered in combination with biologics for the therapy of Rheumatoid Arthritis (RA) as it leads to superior outcomes compared to biologic monotherapy. However, combination therapy may not be tolerated or may be associated with lower adherence.

Objective: To determine whether discontinuation of MTX from the combination regimen with adalimumab (ADA) will lead to inferior outcomes compared to continuation of both medications.

Methods: RA patients enrolled in the Corrona Registry who initiated ADA in combination with MTX were included in the analysis. Patients who discontinued MTX (MTX-DC) after at least three months of combination therapy with ADA were compared with patients who continued combination therapy (MTX-C). Baseline characteristics of both groups were described. Patients in the two groups were matched (1:3) using Propensity Scores (PS) on time from initiation to time to MTX discontinuation in the MTX-DC group and for a similar time point in the MTX-C group.   Disease activity based on clinical disease activity index (CDAI) and patient reported outcomes (patient pain, fatigue, morning stiffness and disability index measured by modified health assessment questionnaire) were compared 6 months after the discontinuation of MTX and an equivalent time in the combination group. Multivariate regression was used to evaluate the aforementioned outcomes adjusted for statistically significant variables after PS matching.

Results:   137 MTX-DC patients were matched with 411 MTX-C patients. MTX-DC patients were more frequently females (82.5% vs 73.2%) and had shorter disease duration (mean±SD: 6.15±7.0 vs 8.03±8.84) compared to the MTX-C group, p<0.05. Baseline disease activity, rates of RF positivity, prior biologic use and concurrent steroid use did not differ between the two groups. Adjusted disease activity improvement outcomes at 6 months did not differ in the two groups; rates of achievement of low disease activity (CDAI≤10) were 39.7% vs 41.6% (p=0.7), minimal clinically important difference (MCID) for CDAI¹ was achieved by 58.6% vs 61.6% (p=0.8) in MTX-C vs MTX-DC respectively. Methotrexate discontinuation was not significantly associated with change in CDAI (Beta-Coefficient, β (95% CI):  0.29 (-1.7 – 2.3). Adjusted patient reported outcomes were similar at 6 months for both groups (Table).

Conclusion: Methotrexate discontinuation after at least 3 months of combined therapy with adalimumab was not associated with inferior disease activity and patient reported outcomes after 6 months of discontinuation of MTX.

References:

1.       Curtis JR et al. 2015. doi: 10.1002/acr.22606.