Effect of initiating biologics compared to intensifying conventional DMARDs on clinical and MRI outcomes in established rheumatoid arthritis patients in clinical remission: Secondary analyses of the IMAGINE-RA trial.

OBJECTIVES: To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. METHOD: One-hundred patients with established RA, Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. RESULTS: Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0-2.6), HAQ score (0.08, 0.03-0.1), MRI combined inflammation (2.5, 0.9-4.1), and SDAI scores (2.7, 1.9-3.5). CONCLUSIONS: Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01656278.

Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethasone with or without additional cyclosporin on MRI-assessed synovitis, osteitis, tenosynovitis, bone erosion, and joint space narrowing in early rheumatoid arthritis: results from a 2-year randomized double-blind placebo-controlled trial (CIMESTRA).

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.

Evaluation of three scoring methods for Fluorescence Optical Imaging in erosive hand osteoarthritis and rheumatoid arthritis.

Objective: Fluorescence Optical Imaging (FOI) demonstrates indocyanine green (ICG)-enhanced microcirculation in wrist and finger joints, as a sign of inflammation. We wanted to assess the reliability of three FOI scoring methods from Berlin, Stockholm, and Copenhagen, to assess the validity of FOI with MRI as reference and to compare enhancement in hand joints in erosive hand osteoarthritis (OA) vs. rheumatoid arthritis (RA). Design: Five readers scored all finger and wrist joints of 26 patients with erosive hand OA and RA on semi-quantitative 0-3 scales using three different FOI scoring methods. To evaluate inter-reader reliability, we calculated the intraclass correlation coefficients (ICC) for sum scores and prevalence and bias adjusted kappa values for ordinal scales (Pabak-OS) on joint level. Enhancement in joint groups in erosive hand OA vs. RA was compared using Mann-Whitney test. Sensitivities and specificities of FOI was calculated with MRI as reference for hand OA patients only. Results: We found moderate to good inter-reader reliability for all FOI scoring methods (Pabak-OS: 0.50-0.78, ICC: 0.43-0.85) and different patterns of enhancement in erosive hand OA vs. RA with significantly more FOI enhancement in DIP joints in erosive hand OA across all methods. With MRI as reference the different FOI scoring methods reached similar sensitivities (63-65%) and specificities (76-91%). Conclusion: FOI enhancement can be measured reliably in erosive hand OA and RA using three different scoring methods. More DIP enhancement in erosive hand OA patients and good agreement with MRI support the diagnostic performance of FOI.