Infliximab in combination with methotrexate in active ankylosing spondylitis. A clinical and imaging study

Helena Marzo-Ortega ¹, Dennis McGonagle ¹, Steve Jarrett ¹, Glenn Haugeberg ², Elizabeth Hensor ¹, Philip O'Connor ³, Ai Lyn Tan ⁴, Philip G Conaghan ¹, Adam Greenstein ¹ and Paul Emery ^1*

¹ Academic Unit of Musculoskeletal Disease. University of Leeds, United Kingdom
² Oslo City Department of Rheumatology. Diakonhjemmet Hospital, Norway
³ Department of Radiology. Leeds General Infirmary, United Kingdom
⁴ Academic Unit of Musculoskeletal Disease. University of Leeds, United Kingdom

^* To whom correspondence should be addressed. E-mail: p.emery{at}leeds.ac.uk.

Accepted 5 April 2005

Abstract

Background and Aims: Infliximab monotherapy is an effective treatment for ankylosing spondylitis (AS) but in RA its efficacy is increased and toxicity decreased when used in combination with methotrexate. The aims of this study were to examine the efficacy and safety of infliximab combined with methotrexate versus methotrexate alone in the treatment of AS. Magnetic resonance imaging (MRI) and bone densitometry (DXA) were performed to monitor its impact on bone.

Methods: In this single centre study 42 subjects with active AS were treated with methotrexate and were randomly assigned to receive 5 infusions of either 5mg/kg infliximab or placebo over a 30 week period with a 2:1 randomisation in favour of the combination arm. The primary outcome was improvement in disease activity as shown by the BASDAI at week 30. MRI was used to assess the effect of therapies on sacroiliac and spinal enthesitis/osteitis and DXA was used to monitor bone mineral density (BMD).

Results: Both therapeutic agents were well tolerated with no dropouts due to adverse events. A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 (p=0.017) compared to the placebo arm, but this was not maintained by week 30 (p=0.195), eight weeks after the last infusion (week 22) at which stage disease flares were reported by some patients. On MRI, the mean number of lesions that resolved per patient from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group (p=0.016).

Conclusions: Infliximab in combination with methotrexate was a safe and efficacious therapy in AS over a six- month period and was associated with significant regression of MRI determined enthesitis/osteitis. However disease flares were reported 8 weeks after last infusion indicating that the addition of methotrexate failed to extend the infliximab dosing interval.

Keywords: MRI, ankylosing spondylitis, imaging, infliximab, methotrexate

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