Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors

Abstract

Introduction: The long-term treatment of rheumatoid arthritis (RA) most often involves a sequence of different therapies. The response to therapy, disease progression and detailed knowledge of the role of different therapies along treatment pathways are key aspects to help physicians identify the best treatment strategy. Thus, understanding the effectiveness of different therapeutic sequences is of particular importance in the evaluation of long-term RA treatment strategies. The objective of this study was to systematically review and quantitatively evaluate the relationship between the clinical response to biologic treatments and the number of previous treatments with tumor necrosis factor α (TNF-α) inhibitors.

Methods: A systematic search was undertaken to identify published, peer-reviewed articles that reported clinical outcomes of biologic treatment among RA patients with an inadequate response to TNF-α inhibitors. Data were systematically abstracted. Efficacy rates were estimated for groups of patients who differed in the number of prior TNF-α inhibitors used. End points included American College of Rheumatology (ACR)-, European League Against Rheumatism (EULAR)- and Disease Activity Score 28 (DAS28)-based response criteria.

Results: The literature search identified 41 publications, of which 28 reported biologic treatment outcomes for RA patients with prior exposure to TNF-α inhibitors. Seven publications reported outcomes obtained in randomized clinical trials, while the remaining consisted of observational studies. The likelihood of responding to a subsequent biologic treatment decreased as the number of previous treatments with TNF-α inhibitors increased for six of the seven response criteria examined.

Conclusions: For patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors.

Figure 1

Percentage of patients achieving a response according to biologic treatment number. Bar graphs showing the percentage of patients achieving a response to any biologic disease-modifying antirheumatic drug (DMARD) according to criteria commonly used in rheumatoid arthritis (RA) patients, separated by number of biologic DMARDs to which the patients were exposed. With regard to the ACR categories, ACR20 means a 20% improvement in tender or swollen joint counts as well as 20% improvement in at least three of the following five criteria: patient assessment, physician assessment, erythrocyte sedimentation rate, pain scale and functional questionnaire. The ACR50 and ACR70 categories adhere to the same criteria, but for 50% and 70% improvement, respectively. ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; DAS28, Disease Activity Score 28 joint count.

Figure 2

Percentage of patients achieving a response by biologic type or study type and biologic number. (a) Bar graphs showing the percentage of patients achieving the American College of Rheumatology ACR20, ACR50 or ACR 70 criteria (see description of these criteria in Figure 1 legend), as well as remission (DAS28 <2.6) or low disease activity (DAS28 ≤3.2) according to the number of biologic disease-modifying antirheumatic drugs (DMARDs) to which the patients were exposed and whether the drug switched to was a tumor necrosis factor (TNF)-α inhibitor or a different type of biologic agent (Other). ACR20, ACR50 and ACR70 rates are based on 8 mg/kg tocilizumab, and DAS28 <2.6 and DAS28 ≤3.2 are based on abatacept. (b) Bar graphs showing the percentage of patients achieving ACR-based improvement criteria according to the number of biologic DMARDs to which the patients were exposed and type of study design. RCT, randomized controlled trial; Observational, observational study.

Figure 3

Percentage of patients responding to a second TNF-α inhibitor by reason for discontinuation of first. Bar graph showing the percentage of patients achieving a response to a second tumor necrosis factor (TNF)-α inhibitor according to criteria commonly used in rheumatoid arthritis by reason of discontinuation of the initial TNF-α inhibitor. ACR, American College of Rheumatology (see Figure 1 legend for description of ACR20, ACR50 and ACR 70 criteria); DAS28, Disease Activity Score 28 joint count; EULAR, European League Against Rheumatism.