Elsevier

Clinical Therapeutics

Volume 33, Issue 7, July 2011, Pages 901-913
Clinical Therapeutics

Pharmaceutical economics & health policy
Review article
Measurement and Rates of Persistence With and Adherence to Biologics for Rheumatoid Arthritis: A Systematic Review

https://doi.org/10.1016/j.clinthera.2011.06.001Get rights and content

Abstract

Background

Biologics are an important addition to the conventional care of patients with rheumatoid arthritis (RA). Poor persistence with and adherence to biologics can undermine the effectiveness of these medications. There are no standardized methods to track persistence with and adherence to biologics.

Objective

The goal of this systematic review was to assess the methods of measurement and reported rates of persistence with and adherence to biologic regimens in patients with RA in clinical practice.

Methods

Observational studies that evaluated persistence with and adherence to biologic treatments in patients with RA were identified by searching Medline and SCI-Expanded for observational studies published in English between January 1995 and May 2009, using the following search terms: adalimumab, adherence, arthritis, biologics, compliance, discontinuation, etanercept, infliximab, persistence, RA, treatment retention, and TNF. The articles were independently reviewed to identify relevant studies and abstracted data.

Results

Of the 52 studies identified, 73% were based in Europe and 21% were set in the United States. All but 1 study reported measures of persistence, such as median drug survival and rates of discontinuation and retention. Four studies reported on adherence, all of which were conducted in the United States and used administrative claims data. Methods of persistence and adherence measurement were unclear or, if recorded, varied considerably across studies. Although various continuation rates (persistence) were reported across studies, the overall range of continuation at 12 months was 32.0% to 90.9%. Continuation rates were generally higher with the addition of methotrexate or other disease-modifying antirheumatic drugs.

Conclusion

The data from the available studies on RA treatments suggest a need for better methods for tracking persistence and adherence, for examining prescribing patterns, and for identifying interventions to improve adherence.

Introduction

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory arthritis that if left untreated may result in severe joint damage and loss of function.1 Biologic treatments have been assessed in individuals with RA.2 Although NSAIDs, conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate and sulfasalazine, and corticosteroids have been the cornerstones of therapy for many years, newer DMARD biologics such as the anti–tumor necrosis factor (TNF)-α agents have been associated with RA remission—the least amount of disease activity by tender and swollen joint counts (Table I).2 Hence, patients and physicians have been willing to assume risks such as infections that may accompany the use of these treatments.2

Poor adherence due to nonclinical factors such as inefficacy, adverse events, or remission, however, may undermine the potential therapeutic benefits of biologics by contributing to treatment failure, progression of disease, and the need for more aggressive treatment.3 Poor adherence further strains already limited health care resources; incomplete treatment provides few or no benefits, and the costs of even partial treatments are high given the expense of the biologics.4 Nonadherence also raises concerns for the insurers and payers responsible for the costs of these agents and the medical costs of disease progression and more aggressive treatment. Therefore, it is clinically and economically important to assess persistence with and adherence to biologic regimens in the RA population.

Methods for measuring persistence with and adherence to oral medications are well established because the majority of oral medications have predictable daily dosing schedules.5, 6, 7, 8 Biologics, however, have complex dosing schedules, and dosages and frequency of dosing are often altered during treatment (Table I). The objective of this review was to summarize the methods used to measure, and the reported rates of, persistence with and adherence to biologic regimens in patients with RA.

Section snippets

Methods

A literature search was conducted to identify studies that measured rates of persistence with and adherence to biologic regimens in patients with RA in clinical practice. In general, the term persistence refers to continuation of drug use for an overall duration of drug therapy (eg, 12 months), and adherence refers to the extent of drug use during a period of persistence (eg, 12 weeks).9 Continuation rate, retention rate, and drug survival are measures of persistence; mean medication possession

Results

Fifty-two studies met the selection criteria. Although all were original studies, 2 were published in letter format.10, 11 Table II summarizes the main characteristics of the included studies.

Discussion

Of the studies included in this review, several assessed adherence to biologics in patients with RA, but most assessed only persistence. Persistence is an important measure that adds the dimension of time to understanding the patterns of use of pharmacotherapies. It usually represents the time over which a patient continues administration based on prescription claims, or the time from the initial fill of the medication until the patient discontinues refills. However, adherence also helps to

Conclusions

Persistence with and adherence to biologic regimens in patients with RA in clinical practice has been measured in multiple studies; however, the methods for measuring the 2 end points have been poorly defined and/or inconsistent from study to study. Most of the findings included in the present review were based on registry data from Europe, with relatively few studies from the United States. The findings highlight the need for better methodologies to track persistence with and adherence to

Acknowledgments

This study was supported by an investigator-initiated research grant from Abbott Laboratories Inc, Abbott Park, Illinois. Dr. Doshi has served on the health economics advisory boards of Amgen Inc, Thousand Oaks, California, and Bristol-Myers Squibb Company, New York, New York.

The authors have indicated that they have no other conflicts of interest with regard to the content of the article. Dr. Blum was responsible for the study design, literature search, data abstraction, interpretation, and

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