WASHINGTON, DC — In patients with early rheumatoid arthritis (RA) with a poor response to methotrexate, adding adalimumab reduces disease activity and prevents further radiographic progression, a post hoc analysis of the double-blind randomized OPTIMA trial reported at the 2016 American College of Rheumatology Annual Meeting.

In patients with early RA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), preferably methotrexate, are recommended as first-line therapy, Josef S. Smolen, MD, division of rheumatology at the Medical University of Vienna and Hietzing Hospital, Vienna, Austria, and colleagues noted. For patients who remain in moderate to high disease activity despite conventional synthetic DMARDs, tumor necrosis factor alpha (TNF) inhibitors represent a potential treatment option.

The 78-week OPTIMA study (Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis, ClinicalTrials.gov Identifier: NCT00420927) evaluated clinical, functional, and radiographic outcomes of adalimumab versus placebo when added to methotrexate in a subgroup of insufficient responders to methotrexate with early RA who experienced rapid radiographic progression and/or remained in high disease activity.

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The analysis included patients who received placebo plus methotrexate for 26 weeks (Period 1) and did not achieve stable low disease activity on DAS28-CRP <3.2 at weeks 22 and 26. These patients, defined as being methotrexate insufficient responders, received open-label adalimumab plus methotrexate for a subsequent 52 weeks (Period 2).

At week 26, the patients were categorized by whether they experienced rapid radiographic progression, defined by change from baseline in modified total Sharp score (mTSS) >1.5 and by disease activity, with high disease activity defined as a DAS28-CRP ≥5.1 and moderate disease activity as 3.2≤ DAS28-CRP <5.1. For each subgroup, baseline values and changes from baseline in DAS28-CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), health assessment questionnaire disability index (HAQ-DI), and mTSS were analyzed.

Results showed that 348 (75.7%) of patients who received placebo plus methotrexate did not achieve stable low disease activity and subsequently received open-label adalimumab plus methotrexate for up to 52 weeks. Among the methotrexate insufficient responders, 64 (18.5%) experienced rapid radiographic progression during Period 1, with 111 (31.9%) in high disease activity and 202 (58.0%) in moderate disease activity.

Patients experiencing rapid radiographic progression had significantly higher mean baseline DAS28-CRP (P=0.003), SDAI (P=0.017), and mTSS (P=0.013) measures compared with patients without rapid radiographic progression.

After adalimumab was added, mean DAS28-CRP and SDAI decreased in those with rapid radiographic progression to levels comparable with those observed in patients without rapid radiographic progression, while mean mTSS did not progress further in both groups, they found.

Patients who were methotrexate insufficient responders who remained in high disease activity—compared with those in moderate disease activity—had significantly higher mean baseline disease activity scores and less clinical and functional improvements at week 26, indicating that high baseline activity may be a predictor of poor response to initial treatment with methotrexate.

“Importantly, regardless of week 26 disease activity status, the addition of adalimumab resulted in a decrease in mean disease activity and HAQ-DI,” Dr. Smolen reported. Among patients who began Period 2 in moderate (but not high) disease activity, mean disease activity scores fell below the low disease activity threshold after 52 weeks of open-label adalimumab plus methotrexate therapy.

During the 26 weeks of exposure to methotrexate, nearly 20% of patients accumulated radiographic damage. Within this group of patients, identifying unique characteristics “may allow for a differential therapeutic approach to preserve structural integrity,” the study concluded.


Smolen JS, van Vollenhoven RF, Wolfe BA, Chen S, Suboticki JL, Kavanaugh A. Adalimumab (HUMIRA) halts radiographic progression and reduces disease activity in patients with a poor initial response to methotrexate.Presented at: ACR/ARHP Annual Meeting; November 11-16, 2016; Washington D.C. Abstract #593.

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This article originally appeared on MPR