The Belgian MIRA (MabThera In Rheumatoid Arthritis) registry: clues for the optimization of rituximab treatment strategies

This study describes the results of the Belgian 'MabThera In Rheumatoid Arthritis (MIRA)' registry: effectiveness, safety and evaluation of the current retreatment practice on the background of the Belgian reimbursement criteria for rituximab

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor

First Validation of the Full PROMIS Pain Interference and Pain Behavior Item Banks in Patients With Rheumatoid Arthritis

Objective: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient-reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch-Flemish PROMIS pain interference (PROMIS-PI) and the PROMIS pain behavior (PROMIS-PB) item banks in patients with RA. Methods: A total of 2,029 patients with RA completed the full PROMIS-PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS-PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross-cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects. Results: The PROMIS-PI and PROMIS-PB banks were sufficiently unidimensional (Omega-hierarchical [Omega-H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3–1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross-cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively). Conclusion: Both PROMIS-PI and PROMIS-PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice

Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial)

Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA