Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?

Abstract

Background: Recent studies with infliximab indicate the therapeutic potential of tumour necrosis factor alpha blockade in spondyloarthropathy (SpA). Because defective host defence is implicated in the pathogenesis of SpA, the potential side effects of this treatment due to impact on the antimicrobial defence are a major concern.

Objective: To report systematically the adverse events seen in a large cohort of patients with SpA treated with infliximab, with special attention to bacterial infections.

Patients and methods: 107 patients with SpA were treated with infliximab for a total of 191.5 patient years. All serious and/or treatment related adverse events were reported.

Results: Eight severe infections occurred, including two reactivations of tuberculosis and three retropharyngeal abscesses, and six minor infections with clear bacterial focus. One patient developed a spinocellular carcinoma of the skin. No cases of demyelinating disease or lupus-like syndrome were seen. Two patients had an infusion reaction, which, however, did not relapse during the next infusion. Finally, three patients with ankylosing spondylitis developed palmoplantar pustulosis. All patients recovered completely with adequate treatment, and infliximab treatment had to be stopped in only five patients with severe infections.

Conclusions: Although the global safety of infliximab in SpA is good compared with previous reports in rheumatoid arthritis and Crohn's disease, the occurrence of infections such as tuberculosis and retropharyngeal abscesses highlights the importance of careful screening and follow up. Focal nasopharyngeal infections and infection related symptoms, possibly induced by streptococci, occurred frequently, suggesting an impairment of specific host defence mechanisms in SpA.

Figure 1

CT scan of the neck in a patient with PsA developing a retropharyngeal abscess during infliximab treatment: flegmonal myositis of the left m. sternocleidomastoideus with an abscess in the retropharynx and anterior of the large blood vessels. The myositis extends to the m. sternohyoideus, m. sternothyroideus, and m. omohyoideus of the left and right neck region and even to the right m. sternocleidomastoideus.

Figure 2

Skin biopsy of a patient with AS who developed palmoplantar pustulosis, showing enlarged epidermis with ortho- and parakeratosis and perivascular infiltration by lymphocytes. There is no clear spongiosis. Haematoxylin-eosin staining, magnification x160.