Elsevier

Joint Bone Spine

Volume 77, Issue 4, July 2010, Pages 325-329
Joint Bone Spine

Original article
Maintained clinical response of infliximab treatment in ankylosing spondylitis: A 6-year long-term study

https://doi.org/10.1016/j.jbspin.2010.02.014Get rights and content

Abstract

Objectives

To investigate the efficacy, safety and drug discontinuation in patients with ankylosing spondylitis treated with infliximab, as well as the drug survival over a period of 6 years.

Methods

Forty patients with ankylosing spondylitis treated with infliximab were included in this open label study. All patients fulfilled the New York revised criteria for ankylosing spondylitis. Infliximab was given intravenously (5 mg/kg/body weight) at weeks 0, 2, 6 and every 8 weeks thereafter for a period of 6 years. Data concerning infliximab efficacy, tolerability, adverse events and drug discontinuation, were recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index 50% and the Ankylosing Spondylitis Assessment Study Group 20% and 40% were also recorded.

Results

A significant improvement in the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Assessment Study Group scores was noted in the first year which sustained through the sixth year of treatment. More specifically, after the sixth year of treatment, Bath Ankylosing Spondylitis Disease Activity Index 50% was achieved by 65% of patients (26/40), Ankylosing Spondylitis Assessment Study Group 20% by 72.5% (29/40) and Ankylosing Spondylitis Assessment Study Group 40% was reached by 70% (28/40) of patients. Clinical improvement was associated with the reduction of acute phase reactants, such as C-reactive protein levels. After the first and the second year of treatment, the survival rate of infliximab reached 95%, after the third year it was 80%, while after the fourth year it was 72.5%, which was maintained throughout the fifth and sixth year of therapy. Five patients were increased the dose of infliximab and three of them had shortened the interval infusion. Overall, 11 patients were withdrawn during the observational period, three because of adverse events, two because of lack of efficacy, while six were lost from follow-up.

Conclusion

Infliximab was effective, safe and well-tolerated in patients with ankylosing spondylitis. The clinical response was maintained for a period of 6 years, with high infliximab survival rate, reaching the percentage of 72.5%.

Introduction

Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease with a prevalence of about 0.1–1.1% of the Caucasian adult population worldwide [1], [2]. It affects mostly young patients in the second and third decade of life [3]. The areas predominantly involved in AS are the spine, the sacroiliac joints and the entheses [4], [5] but patients suffering from AS may also have associated peripheral arthritis or extraarticular involvement, mainly uveitis and inflammatory bowel disease [6]. Therapeutic options for patients suffering from the more severe forms of SpA have been limited during the last decades. Non-steroidal anti-inflammatory drugs (NSAIDs) and physiotherapy have been the basis for AS therapy in order to ameliorate spinal pain. None of the disease-modifying antirheumatic drugs (DMARDs) has shown efficacy in axial disease [7], [8], with the exception of sulfasalazine that has demonstrated some limited effect in patients with AS who had peripheral involvement [9]. Inflammation at the interphase of cartilage and bone has been demonstrated by magnetic resonance imaging (MRI) [10], [11], [12] and by immunohistological investigations of sacroiliac joint biopsies [13], [14], [15]. Moreover, it has been shown that tumor necrosis factor (TNF) α messenger RNA and protein were present in the inflamed sacroiliac joints of patients with early AS [13], [16]. Therefore, therapeutic agents that target the pro-inflammatory cytokine TNFα arose as new alternative AS treatment options. Infliximab, a chimeric monoclonal IgG1 antibody is one of the three main biological agents targeting TNFα. The short-term efficacy of infliximab has been demonstrated in several studies on patients with AS but long-term treatment data are scarce [17], [18], [19], [20], [21]. Recently we reported on the beneficial effects of infliximab treatment, with an infliximab survival of 77.9% [22]. Here, we investigate infliximab efficacy, toxicity and reasons for drug discontinuation during long-term disease course in an open label observational study of patients with active AS.

Section snippets

Methods

Forty patients with AS according to the New York revised criteria [23] were enrolled between January 2003 and July 2003. All patients had active axial spondyloarthropathy and they were given infliximab (5 mg/kg/body weight) intravenously at weeks 0, 2, 6 and every 8 weeks thereafter. If the clinical response was insufficient, the interval between the infusions was shortened to 6 weeks. All patients were followed up according to a standardized protocol which has been approved by the Institutional

Results

All 40 patients who took part in this observational study were eligible for anti-TNF therapy. They all had negative pure protein derivative skin test and normal chest radiographs. They were all presented with axial spondyloarthropathy, while nine of them had simultaneously peripheral joint disease and seven out of the 40 patients had a history of uveitis. Table 1 shows the clinical and demographic data of our patients at baseline. They were all 40 of them men with mean age 41.3 (±10.5) and a

Discussion

This study was conducted to investigate primarily the efficacy and safety of infliximab, but moreover to evaluate the durability of response to infliximab therapy. In the study reported herein, efficacy endpoints were confirmed. The BASDAI 50% improvement was found to be similar throughout the entire observation period with high proportions of patients fulfilling this response criterion at the end of the sixth year (65%). Furthermore, the mean BASDAI scores showed ongoing improvements over this

Conflict of interest statement

The authors have no conflict of interest to declare.

References (33)

  • B. Roychowdhury et al.

    Is methotrexate effective in ankylosing spondylitis?

    Rheumatology (Oxford)

    (2002)
  • M. Dougados et al.

    Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study

    Arthritis Rheum

    (1995)
  • D. McGonagle et al.

    Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy

    Arthritis Rheum

    (1998)
  • J. Braun et al.

    Use of dynamic magnetic resonance imaging with fast imaging in the detection of early and advanced sacroilitis in spondylarthropathy patients

    Arthritis Rheum

    (1994)
  • B. Muche et al.

    Anatomic structures involved in early- and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging

    Arthritis Rheum

    (2003)
  • J. Braun et al.

    Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis

    Arthritis Rheum

    (1995)
  • Cited by (0)

    View full text