Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study

Abstract

Objective: To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis (AS) using MRI and DXA 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, in a ratio of 2:1, to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks. The primary outcome was improvement in disease activity as shown by the BASDAI at week 30. MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density.

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) than in the placebo arm, but this was not maintained by week 30 (p = 0.195), 8 weeks after the last infusion, at which stage disease flares were reported by some subjects. MRI showed that the mean number of lesions resolving for each subject 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 treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI. However, disease flares were reported 8 weeks after the last infusion, indicating that addition of methotrexate failed to extend the infliximab dosing interval.

Figure 1

Randomisation, reasons for treatment discontinuation, and numbers of patients who completed the 30 week study period. ITT, intention to treat.

Figure 2

Analysis of CRP results at all study visits examining the subset of patients in the infliximab treated group who reported a flare of disease in the interim visits.

Figure 3

(A) ASAS20 and (B) ASASBIO (composite ASAS response criteria for biological agents) responses.

Figure 4

Association between change in BASDAI score and numbers of lesions resolved.

Figure 5

DXA results.

Figure 6

Magnetic resonance images of spine and sacroiliac joints before and after treatment. (A) T₂ weighted fat suppressed sagittal sequence of the lumbar spine of a patient showing acute Romanus lesions (thin white arrows) at the anterior inferior aspects of L1 and L3, and anterior superior aspects of L2 and L4 vertebral bodies; (B) complete resolution of the lesions after treatment with infliximab and methotrexate; (C) T₂ weighted fat suppressed coronal oblique image of the SIJ of another patient showing active sacroiliitis (thick white arrow) and (D) marked improvement after treatment with infliximab and methotrexate.