Abatacept More Effective in bDMARD-Naive Patients With RA

Janis C. Kelly

January 30, 2020

"Real-world" data from the Swedish Rheumatology Quality register show that patients with rheumatoid arthritis (RA) for whom abatacept (Orencia, Bristol-Myers Squibb) is the first biologic disease-modifying antirheumatic drug (bDMARD) are more likely to continue treatment and to have good clinical outcomes than those with prior DMARD exposure and/or more active disease.

The researchers further report in an article published online January 22 in Arthritis Research and Therapy that men were more likely than women to continue abatacept and to have a major clinical response.

Rheumatologist Carl Turesson, MD, told Medscape Medical News, "Our findings suggest that you may underestimate the efficacy of a new bDMARD based on the experience from treatment of patients with refractory disease. Most drugs do better in patients with relatively early disease. The challenge is to identify the right drug for early treatment of each patient." Turesson is a professor and senior consultant in rheumatology at Lund University, Malmö, Sweden.

Maxime Dougados, MD, Rheumatology Department, Hôpital Cochin, Paris, France, who was not involved in the study, told Medscape Medical News, "I am personally convinced that abatacept is a very effective drug, probably safer in terms of infections than other biologics. However, I would not propose to change the current EULAR [European League Against Rheumatism] recommendation based on this study."

The researchers used data on 2716 patients with RA from the register, which covers 87% of Swedish patients who are taking bDMARDs. They included all patients with RA for whom treatment with abatacept was initiated between April 2006 and November 2017. At baseline, 17% were biologic-naive, 27% had taken one previous bDMARD, and 56% had taken at least two bDMARDs.

Median disease duration was 14.2 years at abatacept initiation. Most patients had active disease. The mean Disease Activity Score 28–joint count C-reactive protein value was 4.66, and the mean Health Assessment Questionnaire Disability Index (HAQ-DI) was 1.25. Among biologic-naive patients, disease duration was shorter (mean, 9.5 years). These patients were less likely to be currently taking glucocorticoids and were less likely to be treated with intravenous rather than subcutaneous abatacept.

The authors write, "The aim of this study was to describe survival on drug and clinical effectiveness in RA patients treated with abatacept and to investigate predictors of remaining on treatment and having a significant clinical response, in a national cohort." They explain that in some prior studies, register data from several countries had been combined, which raises questions about patient heterogeneity and differences in access to bDMARDs.

The percentage of patients who continued taking abatacept at 6 months and at 12 months was higher for biologic-naive patients (85% and 64%, respectively) than for patients overall (75% and 55%). Continuation rates for patients who had received one or more prior bDMARDs were similar to the overall continuation rates and were significantly lower than for biologic-naive patients. Median time receiving abatacept was significantly longer for biologic-naive patients (2.23 years) than for bDMARD-exposed patients (1.56 – 1.68 years)

Half of abatacept discontinuations were for lack of efficacy, 18.1% were for side effects, 2.5% were for persistent disease remission, and 29.4% were for other reasons. Multivariate analysis showed that abatacept discontinuation was lower among male patients (hazard ratio [HR], 0.86) and among patients taking methotrexate at baseline (HR, 0.85).

The authors report that 24% of the patients had achieved a EULAR good response at 6 months and that 29% had attained such a response at 12 months. Similarly, 59% had achieved a EULAR good or moderate response at 6 months, and 62% had done so at 12 months. Thirty-one percent had achieved an HAQ response at 6 months, and 33% had done so so at 12 months.

Among all patients who initiated abatacept, 21% were still on treatment and had achieved a EULAR good response at 6 months and at 12 months (LUNDEX-corrected EULAR good response). Similarly, 27% were still on treatment and had achieved LUNDEX-corrected HAQ response at 6 months, and 23% had done so at 12 months.

The authors write, "Lack of previous bDMARD exposure, male sex, and a low HAQ score at treatment start were independent predictors of a good clinical response to abatacept both at 6 and at 12 months. Lack of previous bDMARD exposure was also the only predictor of a good functional response both at 6 and at 12 months." They suggest that differences in pain perception might account for some of the difference in outcomes between women and men but note that the relation between sex and treatment response in RA is "far from clear."

Turesson stressed that this study should not be taken to mean that abatacept should be the first-line bDMARD of choice for men with RA, since there was no comparison with other bDMARDs in male patients.

Dougados commented, "I have well understood that this analysis has been conducted thanks to an unrestricted grant from BMS [Bristol-Myers Squibb]. However, I do not understand why the authors have not compared the results obtained with abatacept to the ones obtained with TNF blockers."

The authors conclude, "We demonstrated that bio-naive patients had longer survival on abatacept as well as better clinical and functional response to this drug as compared to bDMARD experienced patients. Sex, and to some extent baseline disease severity, also influenced outcome of treatment with abatacept. Insights on the efficacy and tolerability of abatacept based on such data from a real-life setting may be useful for clinical practice."

"This is a nice study, since long-term observational data are scarce," Josef Smolen, MD, professor of internal medicine and chairman of the Department of Rheumatology, Vienna General Hospital, University of Vienna, Austria, told Medscape Medical News.

"However, there is little novelty here, since it is well established for all bDMARDs, including abatacept and JAK [Janus kinase] inhibitors, that bDMARD-naive patients have better responses than bDMARD-experienced patients. This study does not allow us to conclude that abatacept should be the first bDMARD choice, since the findings pertain to all bDMARDs," Smolen explained. "It also does not say that abatacept should not be the first bDMARD. For many years, the EULAR recommendations have not distinguished between bDMARDs in terms of efficacy and safety; they all have similar benefits and risks," he added.

Turesson said, "We still do not have a reliable method for choosing the best treatment for each patient in early RA, and we don't know whether the sequence of drugs used is important for the outcome in refractory patients."

The study was supported by the Swedish Research Council, Lund University, and Bristol-Myers Squibb. Turesson has received consulting fees from Roche, speaking fees from AbbVie, Bristol-Myers Squibb, Pfizer, and Roche, and an unrestricted grant for this study from Bristol-Myers Squibb. Several coauthors have financial relationships with industry, as indicated in the original article. Smolen and Dougados have disclosed no relevant financial relationships.

Arthritis Res Ther. Published online January 22, 2020. Full text

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