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

Objective: In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. Methods: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. Results: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). Conclusions: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs

Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis

Background: The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). Methods: This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. Results: Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p <  0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p <  0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p <  0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p <  0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression. Conclusions: MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures. Trial registration: ClinicalTrials.gov, NCT01164579

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

CLINICAL OUTCOMES AFTER TWO YEARS OF A TREAT-TO-DRUG-FREE REMISSION STRATEGY WITH TOCILIZUMAB INCLUDING TREATMENT DISCONTINUATION FOLLOWING SUSTAINED REMISSION IN THE ACT-RAY STUDY (ENCORE)

Pathophysiology and treatment of rheumatic disease

CXCL 16 is a surrogate marker of inflammatory bowel disease

Pathophysiology and treatment of rheumatic disease

CLINICAL AND RADIOGRAPHIC OUTCOMES AT TWO YEARS AND THE EFFECT OF TOCILIZUMAB (TCZ) DISCONTINUATION FOLLOWING SUSTAINED REMISSION IN THE SECOND YEAR OF THE ACT-RAY STUDY

Pathophysiology and treatment of rheumatic disease

Proceedings from the 7th Annual International Society for Musculoskeletal Imaging in Rheumatology (ISEMIR) conference

The International Society for Musculoskeletal Imaging in Rheumatology (ISEMIR) was founded in 2005 with the goal of discussing matters related to imaging in rheumatology, particularly, validation, education, and use in clinical practice and research. Because the field of musculoskeletal (MSK) imaging is rapidly evolving, continuous education in the field is imperative. ISEMIR's international faculty and world-renowned experts presented the newest information as it relates to the use of magnetic resonance imaging (MRI) and ultrasound (US) at the 7th annual ISEMIR meeting which took place on April 12-14, 2014 in Santa Monica, California. Presentations from the meeting can be viewed at www.isemir.org

DOUBLE-BLIND STUDY OF TOCILIZUMAB plus METHOTREXATE VERSUS TOCILIZUMAB plus PLACEBO IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS DESPITE PRIOR METHOTREXATE: PROGRESSION OF STRUCTURAL DAMAGE, QUALITY OF LIFE AND PHYSICAL FUNCTION AT 24 WEEKS

Pathophysiology and treatment of rheumatic disease

Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study

Objective: To assess the 1-year efficacy and safety of a regimen of tocilizumab plus methotrexate or placebo, which was augmented by a treat-to-target strategy from week 24. Methods: ACT-RAY was a double-blind, 3-year trial. Adults with active rheumatoid arthritis despite methotrexate were randomised to add tocilizumab to ongoing methotrexate (add-on strategy) or to switch to tocilizumab plus placebo (switch strategy). Tocilizumab 8 mg/kg was administered every 4 weeks. Conventional open-label disease-modifying antirheumatic drugs (DMARDs) other than methotrexate were added at week 24 or later in patients with DAS28>3.2. Results: 556 patients were randomised; 85% completed 52 weeks. The proportion of patients receiving open-label DMARDs was comparable in the add-on (29%) and switch (33%) arms. Overall, week 24 results were maintained or further improved at week 52 in both arms. Some endpoints favoured the add-on strategy. Mean changes in Genant-modified Sharp scores were small; more add-on (92.8%) than switch patients (86.1%) had no radiographic progression. At week 52, comparable numbers of patients had antidrug antibodies (ADAs; 1.5% and 2.2% of add-on and switch patients, respectively) and neutralising ADAs (0.7% and 1.8%). Rates of serious adverse events and serious infections per 100 patient-year (PY) were 11.3 and 4.5 in add-on and 16.8 and 5.5 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3× upper limit of normal were observed in 11% of add-on and 3% of switch patients. Conclusions: Despite a trend favouring the add-on strategy, these data suggest that both tocilizumab add-on and switch strategies led to meaningful clinical and radiographic responses

Proceedings from the 5th Annual International Society for Musculoskeletal Imaging in Rheumatology Annual Conference

Since its inception, ISEMIR has held an annual education meeting highlighting the changes in the utilization of imaging tools for the management of rheumatic diseases. ISEMIR's international faculty and world-renowned experts have discussed these topics at a very high scientific level. The evolution of the content demonstrates the rapidly changing environment in the field of rheumatology. Advances in treatment have led to the increased use of magnetic resonance imaging (MRI) and ultrasound (US). This publication is based upon the proceedings from the 2012 ISEMIR educational meeting that took place on April 26th in Chicago, Illinois. Presentations from the live proceedings can be viewed at www.isemir.org. \ua9 2012 Elsevier Inc