Abatacept Retention Higher Without Prior Biologics

Almost half of patients with rheumatoid arthritis (RA) who initiated treatment with abatacept (Orencia) remained on treatment at 2 years, although retention rates were higher for patients without previous exposure to biologics, European researchers found.

In a multinational cohort of 2,350 patients, the overall retention rate at 2 years was 47.9% (95% CI 45.7-50), according to Reike Alten, MD, of Schlosspark-Klinik University Medicine in Berlin, and colleagues.

But among patients who were biologics-naive, the 2-year retention rate was significantly greater, at 54.5% (95% CI 50.5-58.3) compared with 45.2% (95% CI 42.7-47.7, P<0.001) among those who had already received one or more biologics, the researchers reported in Clinical Rheumatology.

“Abatacept is approved for the treatment of adults with moderate-to-severe RA and, uniquely, exerts a therapeutic effect through interaction with immune cells involved in the pathophysiology of RA by selective modulation of the C28:CD80/CD86 co-stimulation signal that is necessary for full T cell activation,” they explained.

This was a prospective, real-world study known as ACTION that assessed the efficacy, safety, and retention of abatacept in routine care, based on the assumption that patients remaining on a specific treatment have responded without unacceptable toxicity.

Enrollment took place from 2008 to 2013. Mean age was 59, mean disease duration was almost 9 years, and more than three-quarters were women.

A total of 28.6% were biologics-naive, and of the 71.4% who had previous biologics exposure, 43.4% had failed a single biologic and 56.6% had failed two or more.

Among those who were biologics-naive, more had disease duration of 2 years or less (35.7% vs 9%, P<0.001), C-reactive protein was lower (1.7 vs 2.1 mg/dL, P=0.01), and fewer had radiographic erosions already present (58.2% vs 71.5%, P<0.001).

More patients who had previous exposure to biologics initiated abatacept as monotherapy (25.5% vs 16.6%, P<0.001) and also used corticosteroids in dosages above 5 mg/day (54.9% vs 47.3%, P<0.01). The biologics most commonly used were etanercept (Enbrel) and adalimumab (Humira).

Retention rates at 2 years were lower for patients with multiple previous biologics, being 41.3% for those with two or more and 50.2% for those with only a single previous biologic.

Reasons for discontinuation in the biologics-naive group were a lack of efficacy in 61.4% of patients and safety concerns in 21.3%, while in the biologics-failure group, the reasons were the lack of efficacy in 67.7% and safety in 21.2%.

In a multivariate analysis, a predictor of retention in biologics-naive patients was positivity for both rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP), with a hazard ratio of 0.71 (95% CI 0.53-0.96). The presence of diabetes as a comorbidity was associated with a lower likelihood of discontinuation (HR 0.61, 95% CI 0.38-0.99, P=0.043).

A predictor of retention among patients with previous biologics failure was positivity for both RF and anti-CCP (HR 0.76, 95% CI 0.62-0.94, P=0.035), whereas primary efficacy failure showed a trend for greater discontinuation rates (HR 1.28, 95% CI 1-1.63, P=0.014). Combination therapy with methotrexate was less likely to lead to discontinuation (HR 0.68, 95% CI 0.55-0.83, P<0.001), while those with patient global assessment scores of 70 or higher were more likely to have discontinued (HR 1.26, 95% CI 1.05-1.52, P=0.040).

At 2 years, good responses according to the criteria of the European League Against Rheumatism (EULAR) were seen in 57.5% of the biologics-naive group compared with 49.4% of the biologics-failure group, while moderate responses were seen in 33.2% and 32.2%, respectively. No response was reported in 9.3% of the biologics-naive group compared with 18.4% of the biologics-failure group.

The higher rates of good and moderate EULAR responses in the biologics-naive group suggested “a greater benefit with earlier treatment,” the researchers stated.

Serious adverse events were reported in 8.2% of patients, and in 94 cases, resulted in treatment withdrawal. Serious infections developed in 76 patients, malignancies were reported in 24, and 27 patients died, two from opportunistic infections. This was similar to the pattern of adverse events in previous trials, the authors noted.

The finding that seropositivity was associated with greater retention may be explained by a recent study that “demonstrated that abatacept inhibits autoantibody-mediated production of inflammatory cytokines by monocytes via the induction of indoleamine 2,3-dioxygenase.”

“These findings have the potential to inform the development of an individualized treatment plan for the optimal management of patients with moderate-to-severe RA,” they concluded.