Clinical research study
Tumor Necrosis Factor Antagonist Responsiveness in a United States Rheumatoid Arthritis Cohort

https://doi.org/10.1016/j.amjmed.2008.02.018Get rights and content

Abstract

Objective

The study objective was to investigate responsiveness according to whether patients satisfy eligibility criteria from randomized controlled trials of tumor necrosis factor (TNF) antagonists in a multicentered US cohort.

Methods

Biologic-naïve patients with rheumatoid arthritis who were prescribed TNF antagonists (n = 465) in the Consortium of Rheumatology Researchers of North America registry were included. Patients were stratified by whether they met eligibility criteria from 3 major TNF antagonist trials. Two cohorts were examined: Cohort A (n = 336) included patients with complete American College of Rheumatology response criteria except acute phase reactants, and cohort B (n = 129) included patients with complete response criteria. Study outcomes included modified American College of Rheumatology 20% and 50% improvement responses (cohort A) and standard American College of Rheumatology improvement (cohort B).

Results

A minority of patients (5.4%-19.4%) prescribed TNF antagonists met trial eligibility criteria and predominantly had high disease activity (78.5%-100%). For patients who met eligibility criteria in cohort A, rates of 20% improvement (52.3%-63.6%) and 50% improvement (30.8%-45.5%) were achieved. Among patients failing to meet eligibility criteria, rates of 20% improvement (16.2%-20.4%) and 50% improvement (8.9%-10.8%) were consistently inferior (P <.05 all comparisons). For cohort B, similar differences were observed.

Conclusion

This multicentered US cohort study demonstrates that the majority of patients receiving TNF antagonists would not meet trial eligibility criteria and achieve lower clinical responses. These findings highlight the tradeoff between defining treatment responsive populations and achieving results that can be generalized for broader patient populations.

Section snippets

Materials and Methods

Patients with a diagnosis of rheumatoid arthritis and no previous biologic agent use who were enrolled in the registry and prescribed a TNF antagonist for the first time were included. The study period was from March of 2002 to May of 2006. The Consortium of Rheumatology Researchers of North America registry is a prospective observational study of patients with arthritis who were enrolled by participating rheumatologists at both academic and private practice sites; the details have been

Patient and Baseline Disease Activity Characteristics

Baseline characteristics and disease activity levels of patients in cohorts A and B are summarized and compared in Table 1, showing no significant differences with the exception that patients in cohort A were less frequently rheumatoid factor positive (69.8% vs 82.8%, P = .016). Similar proportions of patients prescribed TNF antagonists in cohorts A (27.9%) and B (28.4%) had high Clinical Disease Activity Index scores at baseline. The proportion of patients in cohort A with low, moderate, and

Discussion

In this multicentered US-based cohort study of patients with rheumatoid arthritis who were prescribed TNF antagonists, we had 2 principal findings. First, we observed that less than one fifth of patients with rheumatoid arthritis in the study cohorts prescribed a TNF antagonist would have met the eligibility requirements from 3 major TNF antagonist trials, primarily because of disease activity requirements. The proportion of patients with rheumatoid arthritis satisfying requirements for trial

Conclusions

This study of a large US cohort with rheumatoid arthritis indicates that less than one fifth of patients prescribed TNF antagonists meet typical eligibility requirements from TNF antagonist trials, and that patients failing to meet these criteria achieve inferior responses. These findings highlight the tradeoff between defining a treatment-responsive population and generalizing data from randomized controlled trials to the larger population of patients with rheumatoid arthritis who are treated

Acknowledgment

Dr. Greenberg was supported by Grant Number K23AR054412 from the National Institute of Arthritis And Musculoskeletal And Skin Diseases and a Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation. Dr. Greenberg serves as Chief Scientific Officer for CORRONA.

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    Dr Greenberg was supported by grant number K23AR054412 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and a Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation. Dr Kishimoto was funded by a fellowship grant from the Consortium of Rheumatology Researchers of North America.

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