Study: Adalimumab Monotherapy Provides Benefits Up to 3 Years in RA

Clinical guidelines recommend using conventional disease-modifying anti-rheumatic drugs, like methotrexate, as part of an initial treatment strategy for rheumatoid arthritis (RA). This approach can be followed by a biologic if treatment targets are not met, or if a patient has poor prognostic factors. Combination treatment with a biologic and methotrexate is typically more effective than treatment with methotrexate alone, but some patients may experience adverse events (AEs) with methotrexate that make monotherapy with a biologic a desirable option. While data are becoming more numerous on the feasibility of withdrawing a biologic from a patient who has reached low disease activity (LDA) on combination therapy, data concerning the ability to maintain a treatment target on biologic monotherapy are fewer.

A new, post-hoc study, funded by AbbVie and published in RMD Open, reported that adalimumab, used as monotherapy, led to positive clinical, functional, and radiographic outcomes in patients with RA for up to 3 years in more than half of patients who reached LDA after combination therapy.

The researchers drew from the open-label extension of the phase 3 PREMIER study, in which patients with RA were randomized to receive adalimumab monotherapy, methotrexate monotherapy, or combination therapy with methotrexate and adalimumab. All patients who completed the 2-year study were eligible for the open-label extension, in which they received adalimumab at 40 mg every other week for up to 8 years, with the option to add methotrexate if deemed necessary by the investigator. In total, 183 patients enrolled in the open-label extension, and 140 of them (77%) were in an LDA state at year 2.

According to the current, post-hoc study, 84 patients (60%) used adalimumab alone, while 56 (40%) reinitiated methotrexate in combination with adalimumab during the extension period. A total of 60 patients in monotherapy and 44 patients in combination therapy completed 3 years of treatment. Patients 65 or older were more likely to add methotrexate, and those who reinitiated methotrexate generally had higher measures of disease activity than those who remained on adalimumab monotherapy.

Among those who used methotrexate during the extension, 34 (61%) retained LDA status at year 3, and 48% reached a disease activity score, measured with C-reactive protein (DAS28-CRP), of less than 2.6. Twenty-five (45%) of these patients had normal physical function, and 26 (46%) had no radiographic progression, at year 3.

The majority (n = 53, 63%) of the adalimumab-only patients who entered the extension with LDA maintained this state at year 3. Additionally, 42 (70%) patients achieved a DAS28-CRP score of less than 2.6 at the end of year 3. Forty-nine (58%) of these patients had normal physical function, and 42 (50%) had no radiographic progression at year 3.

Between the 2 groups, the incidence of treatment-emergent AEs was similar, though the rate of AEs leading to treatment discontinuation was numerically higher in the methotrexate group, and 3 malignancies were reported in the adalimumab-only group (versus no malignancies in the methotrexate group).

“Following attainment of an LDA state at year 2 with the combination of adalimumab [plus] methotrexate treatment, adalimumab monotherapy for up to 3 years permitted at least half of the patients to retain LDA with normal physical function and minimal radiographic progression,” conclude the authors. “Methotrexate withdrawal appears possible for some patients once clinical target has been achieved.”

Reference

Keystone EC, Breedveld FC, Kupper H, Li Y, Florentius S, Sainsbury I. Long-term use of adalimumab as monotherapy after attainment of low disease activity with adalimumab plus methotrexate in patients with rheumatoid arthritis. RMD Open. 2018;4:e000637. doi: 10.1136/rmdopen-2017-000637.