TNFα antagonist therapy in ankylosing spondylitis and psoriatic arthritis: recommendations of the French Society for Rheumatology

Abstract

Objectives

To develop recommendations for TNFα antagonist therapy in patients with spondyloarthropathies.

Methods

The Delphi consensus procedure was used to select questions, to which evidence-based answers were sought in the literature. Expert opinion was used when needed to estimate the risks and benefits of TNFα antagonists. TNFα antagonists exert potent antiinflammatory effects but fail to provide a definitive cure.

Results

Recommendations were developed for patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). The following criteria for TNFα antagonist therapy were selected: definitive diagnosis of AS or PsA, active disease for at least 4 consecutive weeks documented during two physician visits, overall physician's assessment of disease activity ≥ 4/10 and BASDAI ≥ 4/10 in axial disease or at least three tender and swollen joints in peripheral disease, failure to respond adequately to at least three nonsteroidal antiinflammatory drugs given in optimal dosages for at least 3 months in axial disease or at least one disease-modifying antirheumatic drug (methotrexate, leflunomide, sulfasalazine) for at least 4 months, with local glucocorticoid injections if appropriate, in peripheral disease. Effectiveness and safety should be evaluated by a rheumatologist. The frequency of monitoring depends on the drug. Lack of effectiveness should be defined as inadequate improvement after 6–12 weeks, with a less than two-point decrease in the BASDAI in axial disease or a less than 30% decrease in the tender and swollen joint counts in peripheral disease.

Conclusion

These clinical practice recommendations should help rheumatologists in their everyday decisions regarding the use of TNFα antagonist therapy in patients with AS or PsA.

Introduction

Spondyloarthropathies are characterized by inflammation of the entheses and a strong association with HLA-B27 [1]. This group of diseases includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), the joint manifestations of chronic inflammatory bowel diseases, reactive arthritis, and undifferentiated spondyloarthropathy [2]. Classification criteria developed by Amor and by the European Spondylarthropathy Study Group (ESSG) cover the entire spondyloarthropathy spectrum [3], [4]. A recent study in France showed that the prevalence of spondyloarthropathies was similar to that of rheumatoid arthritis (RA), i.e. about 0.3% of the general population [5]. The first symptoms usually develop in the third or fourth decade of life, although a few patients experience onset in childhood. In the long-term, spondyloarthropathies cause disability, a deterioration in quality of life, and excess mortality, leading to considerable direct and indirect human costs [6], [7].

The treatment of axial spondyloarthropathies rests on nonsteroidal antiinflammatory drugs (NSAIDs) and physical therapy. In contrast to experience with RA, conventional disease-modifying antirheumatic drugs (DMARDs) have little or no effect on the axial manifestations of spondyloarthropathies [8], [9]. TNFα antagonists were effective in several observational or randomized controlled trials in patients with AS or PsA [10], [11], [12], [13]. Three TNFα antagonists are licensed for use in patients with RA: infliximab, etanercept, and adalimumab. At the time these recommendations were developed (2004), two of these drugs were also licensed for use in AS and PsA; the third obtained approval for these diseases in 2005.

Although TNFα antagonists produce rapid, significant, and lasting symptomatic improvements, they fail to provide a definitive cure. Furthermore, no factors predicting the long-term effectiveness and safety of TNFα antagonists have been identified to date, and the risk–benefit ratio of these drugs is not well known. Therefore, standard practice guidelines are needed, most notably for patient selection and for determining the best modalities of treatment initiation and adjustment. International recommendations have been issued by the Assessment in Ankylosing Spondylitis (ASAS) working group [14], [15] and developed by rheumatology societies in Canada in 2004 [1], Italy [16], and the UK [17]. However, none of these recommendations are sufficiently detailed to be of assistance in everyday practice.

The objective of this study conducted under the aegis of the French Society for Rheumatology and of the Joint Diseases and Inflammation Club (CRI: Club Rhumatismes and Inflammation) was to develop recommendations that would help rheumatologists decide when and how to use TNFα antagonists in patients with spondyloarthropathies seen in everyday practice (Fig. 1).