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

Abstract

ObjectivesTo 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.MethodsIn 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.ResultsIn 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.ConclusionsThese 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 numberNCT01164579.

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

“…In summary, patients aged C 18 years (ORAL Sequel) or C 20 years (A3921041) with a diagnosis of RA based on the American College of Rheumatology (ACR) 1987 Revised Criteria [21] were eligible to enroll in the LTE studies if they had completed a prior qualifying tofacitinib phase I (ORAL Sequel only), phase II, or phase III index study [6][7][8][9][10][11][12][13][14][15][16][22][23][24][25][26], and patients must have received tofacitinib for at least 3 years in the LTE studies to be included in this analysis.…”

Baseline MRI bone erosion predicts the subsequent radiographic progression in early rheumatoid arthritis patients who achieved sustained good clinical response

“…The change in MRI bone erosion during the treatment was not very large, and we did not find a difference between the radiographic progression group and the group with no progression (data not shown). Recent randomized controlled trials of bDMARDs or tafacitinib have shown that the change in the RAMRIS score of bone erosion was small compared with those of synovitis and bone edema [11,15]. Therefore, it might be difficult to obtain a difference in the RAMRIS bone erosion score through DMARDs treatment, especially if the disease activity is well controlled.…”

“…However, recent reports have revealed partial recovery of MRI bone erosion in RA patients treated with bDMARDs or tofacitinib [13][14][15].…”

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

“…Nine RCTs11 13–18 21 22 included follow-up intervals ≤12–16 weeks, and in seven of the nine, MRI demonstrated statistically significant inhibition of progression of bone erosions with active treatment compared with placebo within that time frame14 15 17 18 or showed a lack of inhibition consistent with later X-ray data within the trial16 22 or in subsequent trials 23. Two of the nine RCTs were underpowered, but did show numerical suppression of erosion progression on early MRI (one RCT included only 20–21 patients per arm, and in contrast to the other RCTs, used only a single reader;13 the second RCT included 28–35 patients per arm and showed numerical suppression of MRI erosion relative to placebo at 4 and 12 weeks and statistically significant suppression by 24 weeks) 21…”

“…Two of the nine RCTs discussed above17 21 and an active-comparator trial24 included MRI follow-up intervals of 4 weeks or less. Two of these trials demonstrated statistically significant suppression of synovitis and osteitis with MRI after only 2 weeks of active therapy, using 30–3224 and 30–3117 patients per arm, respectively.…”