Review of treatment response in rheumatoid arthritis: assessment of heterogeneity

Abstract

Objective:

Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients’ physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research.

Research design and methods:

A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table.

Results:

A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time.

Conclusions:

This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.

Key words::

• Antirheumatic agents
• Biologic modifiers
• Drug therapy
• Predictors
• Rheumatoid arthritis
• Treatment outcome

Transparency

Declaration of funding

This study was sponsored by Eli Lilly and Company (Lilly Corporate Center, Indianapolis, IN 46285, USA). As authors, employees of the sponsor were involved in discussions about the study, interpretation of data, and writing of the manuscript.

Declaration of financial/other relationships

I.G., G.C.C., R.A.C., C.I.A., K.L.S., and R.P. have disclosed that they are employees of and hold equity in Eli Lilly and Company. V.Z. and M.L. have disclosed that they are employees of i3 Innovus, which was contracted by the sponsor to conduct the review. All authors had full access to the raw data set and take responsibility for the integrity of the data and the accuracy of the data analysis.

CMRO peer reviewers have disclosed that they have no relevant financial relationships to disclose.

Acknowledgments

The authors thank Sujatha Sundaram, PhD, of i3 Innovus, for her contribution to preparing the first draft and final revision of this paper; Gail Caine, also of i3 Innovus, for assisting with the conduct of literature searches; Kenneth Saag, MD, of the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, for his critical review of the summary report, and the following individuals from the Eli Lilly and Company Global Health Outcomes Organization: James Murray, PhD, Don Buesching, PhD, and Marc Berger, MD (contribution made while at Eli Lilly and Company) for conception and design of the study.