Anti-tumour necrosis factor α therapy for ankylosing spondylitis: international experience

Abstract

The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor α (TNFα) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFα, which have included approximately 300 patients with SpA. Specifically, TNFα-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFα and other emerging biological agents.

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Figure 1 .

(A) Computed tomography (CT) guided sacroiliac biopsy specimens from patients with active AS; (B) provided specimens with TNFα mRNA (black spots).⁵ Adapted and reprinted, with permission from the authors and Wiley-Liss, Inc, a subsidiary of John Wiley and Sons, Inc, from reference 5. Copyright © 1995 Wiley-Liss.

Figure 2 .

Response among patients with AS treated with placebo (n=35) or infliximab 5 mg/kg (n=34) at weeks 0, 2, and 6. (A) >50% Improvement in BASDAI; (b) >50% improvement according to the original ASAS Working Group criteria.⁴⁹ *p<0.0001; p values were calculated by Fisher's exact test. Adapted and reprinted, with permission from the authors and Elsevier Science, from reference 49. Copyright © 2002 by Elsevier Science.

Figure 3 .

(A) Patient and (B) doctor global assessments of disease activity on a 100 mm VAS among patients with SpA receiving placebo (n=20) or infliximab 5 mg/kg at weeks 0, 2, and 6 (n=20).⁵¹ *p=NS; †p≤0.05; ‡p≤0.001; §p≤0.01. Adapted and reprinted, with permission from the authors and Wiley-Liss, Inc, a subsidiary of John Wiley and Sons, Inc, from reference 51. Copyright © 2002 Wiley-Liss.

Figure 4 .

Percentage of patients achieving a clinical response. Group 1 received etanercept injections throughout both studies. Group 2 received placebo injections from day 0 to day 112, then etanercept injections from day 112 to day 280. Clinical response defined as at least 20% improvement in three of five outcome measures. *p=0.01.

Figure 5 .

Sacroiliac joints (SIJ) before (A) and three months after (B) the start of infliximab treatment. Sacoiliitis located in the ventral part of the left SIJ is seen in a T₁ sequence after administration of gadolinium-DTPA (A, arrow) but not, using the same technique at the follow up examination (B, arrow). The spinal MRI before treatment shows spondylitis anterior at vertebrae L2-4 at the lumbar spine (C, arrows), which cannot be seen three months later (D, arrows).⁴⁹ These previously unpublished images are provided courtesy of Dr Matthias Bollow, Augusta Krankenhaus, Bochum and Charité, Humboldt University, Berlin, Germany.