CHICAGO – Most patients with early active rheumatoid arthritis who discontinued adalimumab after achieving stable low disease activity on 26 weeks of combination therapy with methotrexate and adalimumab maintained that response through week 78 of treatment in a randomized, double-blind, placebo-controlled trial.
However, more patients who remained on the combination therapy achieved high levels of disease control, based on measures such as American College of Rheumatology 70% response (ACR70) and disease activity score 28 (DAS28) less than 2.6, which suggests that certain patients will benefit from remaining on combination therapy, according to Dr. Arthur F. Kavanaugh, professor of medicine and director of the center for innovative therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
"The billion dollar question: Can we predict which patients we could [withdraw from a tumor necrosis factor inhibitor] and have absolutely no penalty ... is there a predictor?" said Dr. Kavanaugh, in discussing the implications of the findings of OPTIMA (study of the Optimal Protocol for Methotrexate and Adalimumab combination therapy in early RA) at the annual meeting of the American College of Rheumatology.
After "intense analysis of all manner of baseline characteristics," the answer is that only a low baseline score on the Health Assessment Questionnaire (HAQ) was found to predict which patients would do better with adalimumab withdrawal vs. continuation on combined therapy based on a composite outcome of DAS28 less than 2.6 or Simplified Disease Activity Index (SDAI) score of 3.3 or less and Health Assessment Questionnaire score of less than 0.5 (odds ratio, 1.9), he said.
Study participants were 207 adults aged 18 years or older from the first phase of the study. All had early active severe disease and achieved stable low disease activity defined as a DAS28 less than 3.2 on combination therapy within 26 weeks. For the current phase of the study, the patients were rerandomized to continue combination therapy or to have adalimumab withdrawn for an additional 52 weeks.
The percentage of patients achieving ACR20 and ACR50 responses, indicating 20% and 50% improvements in the signs and symptoms of disease, was 94% and 80% in the patients in whom adalimumab was withdrawn, compared with 95% and 89% in those who continued on combination therapy. The differences between the groups on these outcomes measures were not statistically significant.
Baseline characteristics in the withdrawal and continued combination therapy groups were similar; mean RA duration in both groups was 3.9 months. DAS28 was 5.9 and 5.7 in the withdrawal and continued combination therapy groups, respectively. C-reactive protein levels were 28.4 and 23.5 mg/L, mean 68-joint tender joint counts were 25.5 and 23.3, mean 66-joint swollen joint counts were 16.4 and 15.4, and mean modified total van der Heijde/Sharp scores were 12.2 and 10.8.
No significant difference was seen between the groups in regard to changes in SDAI scores of 11 or less, or in SDAI scores of 3.3 or less. No differences were seen between the groups in regard to radiographic progression as measured by mean modified total van der Heijde/Sharp scores, or in regard to changes in functional status as measured by mean HAQ scores.
The percentage who achieved ACR70, however, was 65% in the adalimumab withdrawal group, compared with 77% in the continued combination therapy group. This difference was statistically significant.
Furthermore, 81% of patients in the withdrawal group achieved DAS28 of less than 3.2, compared with 91% of those in the continued combination therapy group (P = .04), and 66% vs. 86% of patients in the groups, respectively, achieved DAS28 of 2.6 or less (P = .001).
Other than HAQ scores, nothing predicted with any strength who would do well after adalimumab withdrawal – even in univariate analysis, Dr. Kavanaugh stressed.
Dr. Kavanaugh disclosed that he received consulting fees or other remuneration from Abbott Laboratories. Other study authors also disclosed financial relationships with Abbott Laboratories and other companies, including, Bristol-Myers Squibb, GlaxoSmithKline, Merck Pharmaceuticals, MSD, Pfizer, Roche Pharmaceuticals, and/or UCB Pharma.