Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques
Philip G Conaghan, Mikkel Østergaard, Michael A Bowes, Chunying Wu, Thomas Fuerst, Désirée van der Heijde, Fedra Irazoque-Palazuelos, Oscar Soto-Raices, Pawel Hrycaj, Zhiyong Xie, Richard Zhang, Bradley T Wyman, John D Bradley, Koshika Soma, Bethanie Wilkinson, Philip G Conaghan, Mikkel Østergaard, Michael A Bowes, Chunying Wu, Thomas Fuerst, Désirée van der Heijde, Fedra Irazoque-Palazuelos, Oscar Soto-Raices, Pawel Hrycaj, Zhiyong Xie, Richard Zhang, Bradley T Wyman, John D Bradley, Koshika Soma, Bethanie Wilkinson
Abstract
Objectives: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.
Methods: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.
Results: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.
Conclusions: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.
Trial registration number: NCT01164579.
Keywords: DMARDs (synthetic); Inflammation; Magnetic Resonance Imaging; Methotrexate; Rheumatoid Arthritis.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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