Objectives To explore the effects of tofacitinib-an oral Janus kinase inhibitor

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. 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 Rabbit polyclonal to ACAP3. RAMRIQ erosive damage Everolimus 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 Introduction Inflammation of the synovium particularly the bone marrow measured using MRI has been identified as a prognostic indicator of structural joint damage in patients with rheumatoid arthritis (RA).1-3 Inhibition of this damage at an early stage in the disease course is desirable to limit disability4 and impact on general health and quality of life.5 Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of RA. The efficacy and safety of tofacitinib 5 and 10?mg twice daily in patients with active moderate-to-severe RA has been demonstrated in randomised double-blind phase 26-10 and phase 311-16 studies of up to Everolimus 24?months duration and in open-label long-term extension studies with up to 96?months of observation.17 The inhibition of structural damage in patients who received tofacitinib has been shown using plain-film radiography.14 15 MRI measures provide improved sensitivity versus conventional radiography.18-20 Bone marrow oedema (BME) and synovitis measured using MRI have been shown to be highly sensitive to treatment with conventional synthetic disease-modifying antirheumatic drugs.21-25 However few randomised clinical trials have been published using MRI outcomes as primary endpoints in patients with early RA.21 23 26 The validated semiquantitative assessment of multiple pathologies using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI score (RAMRIS)29 has become the standard for MRI trials.20 Quantitative MRI measures offer the opportunity to improve on the responsiveness of semiquantitative scoring. Dynamic contrast-enhanced (DCE) MRI measurements show strong correlation with histological assessments of synovitis30 and have demonstrated sensitivity in detecting therapy-induced Everolimus changes in synovitis in patients with early RA.31 32 Preliminary work with active appearance modelling (AAM)33 RA MRI quantification (RAMRIQ) of all involved joint tissues has suggested improved responsiveness over RAMRIS.34 Patients with early RA have participated in previous studies of tofacitinib although the lowest mean duration of RA was approximately 3?years.14 This is the first study to explore the effects of tofacitinib as monotherapy or in combination with methotrexate (MTX; vs MTX with placebo) on a range of Everolimus highly sensitive MRI endpoints exclusively in patients with early RA. Methods Study design and conduct This was an exploratory phase 2 randomised double-blind double-dummy parallel-group study (A3921068; NCT01164579) conducted at 24 centres in Central and Latin America Europe and the USA (25 October 2010-5 November 2013). Study end was the month 12 visit or early termination for patients who discontinued. Randomisation and treatment At baseline patients were randomised 1:1:1 using an automated web/telephone randomisation system to tofacitinib 10?mg twice daily with MTX tofacitinib 10?mg twice daily with placebo (tofacitinib monotherapy) or MTX with placebo (MTX monotherapy) for 12?months. Tofacitinib 10?mg twice daily was administered orally as two.