Effect of discontinuing TNFα antagonist therapy in patients with remission of rheumatoid arthritis

doi:10.1016/j.jbspin.2008.11.009

Joint Bone Spine

Volume 76, Issue 4, July 2009, Pages 350-355

https://doi.org/10.1016/j.jbspin.2008.11.009 Get rights and content

Abstract

Objective

The objective of this study was to determine the time to relapse after tumor necrosis factor α (TNFα) antagonist discontinuation in patients with remission of rheumatoid arthritis (RA).

Methods

Among 304 patients taking TNFα antagonist therapy for RA, 21 achieved a remission and were taken off the TNFα antagonist. Remission was defined as DAS28 < 2.6 for at least 6 months without nonsteroidal inflammatory drugs or more than 5 mg of prednisone per day but with disease-modifying antirheumatic drug (DMARD) therapy if needed. The same TNFα antagonist was restarted in the event of a relapse (DAS28 > 3.2).

Results

The 21 patients had a mean age of 61 years, a mean disease duration of 11.3 years, and a mean remission duration at TNFα antagonist discontinuation of 19.2 months. The TNFα antagonist was infliximab in 2 patients, adalimumab in 5, and etanercept in 14; and 14 patients were taking a concomitant DMARD. The number of patients still in remission after TNFα antagonist discontinuation was 9/20 after 6 months and 5/20 after 12 months. Mean time to relapse was 14.7 weeks. While off TNFα antagonist therapy, 3 of the 5 relapse-free patients after 12 months were on DMARD therapy, compared to 11 of the 15 patients who relapsed. Compared to the 15 patients who relapsed, the 5 relapse-free patients had a longer time on TNFα antagonist therapy (56 months vs. 35 months, P = 0.012) and a longer time in remission on TNFα antagonist therapy (35 months vs.14.5 months, P = 0.04). The 15 patients who relapsed consistently achieved a remission after resuming TNFα antagonist therapy; the remission occurred within 2 months in 13 patients.

Conclusion

TNFα antagonist discontinuation in patients in remission of RA was followed by a relapse within 12 months in 75% of cases. Relapsing patients responded well to resumption of the same TNFα antagonist.

Introduction

In patients with rheumatoid arthritis (RA), achieving a remission is now a reasonable treatment objective. Among the major therapeutic breakthroughs that have improved outcomes in RA patients in recent years [1] the most notable is the introduction of tumor necrosis factor α (TNFα) antagonists [2], [3], [4]. The proportion of patients in remission ranges from 7% to 25% with conventional disease-modifying antirheumatic drugs (DMARDs) and from 21% to 49% with a TNFα antagonist and methotrexate in combination [5].

Once a remission is achieved, the need for continued TNFα antagonist therapy must be assessed. The dose can be decreased as a preliminary to complete discontinuation [6]. The effects of discontinuing TNFα antagonist therapy after obtaining a remission are poorly understood. Although remission rates are highest in patients with early-stage disease [1], TNFα antagonist therapy can provide remissions in patients with long-standing RA.

The objectives of this study were to identify risk factors for relapse and to measure the time to relapse after TNFα antagonist discontinuation in patients with established RA who had been in remission for at least 6 months. We also evaluated the response of relapses to resumption of the same TNFα antagonist.

Section snippets

Patients

Between August 1999 and June 2005, we assessed TNFα antagonist continuation rates in 442 patients with inflammatory joint disease [7], of whom 304 met American College of Rheumatology criteria for RA [8]. We identified patients who were in remission, defined as a Disease Activity Score on 28 joints (DAS28) lower than 2.6 [9] for at least 6 months, without nonsteroidal anti-inflammatory drugs and with or without prednisone in a daily dosage of less than 5 mg as recommended by the French Society

Results

We identified 304 RA patients treated with a TNFα antagonist between August 1999 and June 2005 (Fig. 1). There were 247 females and 57 males with a mean age of 58 years. The first TNFα antagonist was etanercept in 157 patients, infliximab in 104, and adalimumab in 43. Furthermore, 91 patients had been switched to a second TNFα antagonist, which was etanercept in 53 patients, infliximab in 7, and adalimumab in 31.

In September 2006, 28 (9.2%) patients met our criteria for disease remission (DAS28 <

Discussion

Our study has a number of limitations. First, we were able to include only 21 of 28 patients in remission. These 28 patients represented 9.2% of our population of 304 RA patients. Remission rates in patients with established RA treated with TNFα antagonists ranged in earlier studies from 7% [3] to 24% [4]. Second, we discontinued TNFα antagonists only in patients who remained in remission after stopping their nonsteroidal anti-inflammatory drugs and decreasing their daily prednisone dosage to 5

Conflict of interest:

None of the authors has any conflicts of interest to declare.

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Original articleEffect of discontinuing TNFα antagonist therapy in patients with remission of rheumatoid arthritis

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Patients

Results

Discussion

Conflict of interest:

Joint Bone Spine

Joint Bone Spine

Joint Bone Spine

Remission as the treatment goal—the FIN-RACo trial

Clin Exp Rheumatol

Maintenance therapy for rheumatoid arthritis after remission following successful treatment using biologics

Nippon Rinsho

Minimal disease activity, remission, and the long-term outcomes of rheumatoid arthritis

Arthritis Rheum

GISEA group. Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: the GISEA study

J Rheumatol

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis

Arthritis Rheum

Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization / International League Against Rheumatism Criteria

Arthritis Rheum

OMERACT 7 Special Interest Group. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

J Rheumatol

Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis

Arthritis Rheum

Original article
Effect of discontinuing TNFα antagonist therapy in patients with remission of rheumatoid arthritis