Background/Purpose

Abatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA) that inhibits T cell activation by binding to CD80/86, and modulating its interaction with CD28. Although some reports demonstrated that concomitant methotrexate (MTX) had little enhancing effect on short-term clinical efficacy of ABT, there have been only few long-term studies. We studied whether background MTX treatment enhanced the ABT efficacy after 24 weeks, by using data from Japanese multicenter registry system for RA patients using biological DMARDs.

Methods

All RA patients who underwent ABT treatment for at least 52 weeks (n = 254) in Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Registry Study Group) were enrolled in this study. Demographic data and the following parameters of disease activity were collected; tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels at baseline, 24 weeks, and 52 weeks. We compared these clinical data between the patients treated without concomitant MTX (ABT-mono, n = 130) and those treated with concomitant MTX (ABT-MTX, n = 124, mean MTX dose of 7.4 mg/week). The last observation carried forward (LOCF) method was used in each analysis.

Results

In the baseline characteristic data, the ABT-mono group had higher pulmonary comorbidity rate (21.5 vs 6.5%, p = 0.001) compared to the ABT-MTX group while no other clinical parameters showed significant difference including the proportion of patients with previous biological DMARDs history (47.7 vs 47.6, p = 0.986) or the all disease activity indices such as DAS28 (4.48 and 4.54). As shown in Figure Left and Middle panel, the ABT-MTX group demonstrated statistically significant decreasing of DAS28 from 24 to 52 weeks while no difference in the ABT-mono group. We next studied the patients that still adhered on ABT therapy in spite of their poor clinical efficacy (moderate or high disease activity, DAS28-CRP > 2.7) at 24 weeks. Logistic regression analysis identified the concomitant MTX therapy and female as independent predictors of DAS28 category improvement (e.g. high to moderate disease activity) from 24 to 52 weeks (Figure Right panel).

Conclusion

Concomitant MTX therapy significantly decreased the disease activity after 24 weeks, while it seemed not to have enhancing effect on short-term clinical efficacy of ABT. It is true that the ABT efficacy is still significant even in the patients without MTX usage. However, it would be beneficial to use concomitant MTX in most of RA patients without serious comorbidity for MTX usage.