Identifying Minimal and Meaningful Change in a Patient-Reported Outcomes Measurement Information System for Rheumatoid Arthritis: Use of Multiple Methods and Perspectives.

OBJECTIVE: Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. Our objective was to use different methods and perspectives to evaluate the responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) short forms (SFs) and to identify minimal and meaningful score changes. METHODS: Adults with RA who were enrolled in a multisite prospective observational cohort completed PROMIS physical function, pain interference, fatigue, and participation in social roles/activities SFs, the PROMIS 29-item form (PROMIS-29), and pain and patient global assessment, and rated change in specific symptoms and RA (a little versus lot better or worse) at the second visit. Physicians recorded joint counts, physician global assessment, and change in RA at visit 2. We compared mean score differences for minimal and meaningful improvement/worsening using patient and physician change ratings and distribution-based methods, and we visually inspected empirical cumulative distribution function curves by change categories. RESULTS: The 348 adults were mostly female (81%) with longstanding RA. Using patient ratings, generally 1-3-point differences were observed for minimal change and 3-7 points for meaningful change. Larger differences were observed with patient versus physician ratings and for symptom-specific versus RA change. Mean differences were similar among SF versions. Prespecified hypotheses about change in PROMIS physical function, pain interference, fatigue, and participation and legacy scales were supported. CONCLUSION: PROMIS SFs and the PROMIS-29 profiles are responsive to change and generally distinguish between minimal and meaningful improvement and worsening in key RA domains. These data add to a growing body of evidence demonstrating the robust psychometric properties of PROMIS and supporting its use in RA care, research, and decision-making.

Patient-reported outcomes in RA care improve patient communication, decision-making, satisfaction and confidence: qualitative results.

OBJECTIVE: To evaluate the impact of integrating patient-reported outcomes (PROs) into routine clinics, from the perspective of patients with RA, clinicians and other staff. METHODS: We conducted a prospective cohort study using a mixed methods sequential explanatory design at an academic arthritis clinic. RA patients completed selected Patient-Reported Outcomes Measurement Information System measures on tablets in the waiting room. Results were immediately available to discuss during the visit. Post-visit surveys with patients and physicians evaluated topics discussed and their impact on decision making; patients rated confidence in treatment. Focus groups or interviews with patients, treating rheumatologists and clinic staff were conducted to understand perspectives and experiences. RESULTS: Some 196 patients and 20 rheumatologists completed post-visit surveys at 816 and 806 visits, respectively. Focus groups were conducted with 24 patients, 10 rheumatologists and 4 research/clinic staff. PROs influenced medical decision-making and RA treatment changes (38 and 18% of visits, respectively). Patients reported very high satisfaction and treatment confidence. Impact on clinical workflow was minimal after a period of initial adjustment. PROs were valued by patients and physicians, and provided new insight into how patients felt and functioned over time. Reviewing results together improved communication, and facilitated patient-centred care, shared decision making, and the identification of new symptoms and contributing psychosocial/behavioural factors. CONCLUSION: PRO use at RA visits was feasible, increased understanding of how disease affects how patients feel and function, facilitated shared decision-making, and was associated with high patient satisfaction and treatment confidence.

Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis.

Autoantibodies to citrullinated protein antigens are specific markers of rheumatoid arthritis (RA). Although protein citrullination can be activated by numerous stimuli in cells, it remains unclear which of these produce the prominent citrullinated autoantigens targeted in RA. In these studies, we show that RA synovial fluid cells have an unusual pattern of citrullination with marked citrullination of proteins across the broad range of molecular weights, which we term cellular hypercitrullination. Although histone citrullination is a common event during neutrophil activation and death induced by different pathways including apoptosis, NETosis, and necroptosis/autophagy, hypercitrullination is not induced by these stimuli. However, marked hypercitrullination is induced by two immune-mediated membranolytic pathways, mediated by perforin and the membrane attack complex (MAC), which are active in the RA joint and of importance in RA pathogenesis. We further demonstrate that perforin and MAC activity on neutrophils generate the profile of citrullinated autoantigens characteristic of RA. These data suggest that activation of peptidylarginine deiminases during complement and perforin activity may be at the core of citrullinated autoantigen production in RA. These pathways may be amenable to monitoring and therapeutic modulation.

Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization.

OBJECTIVE: Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures. METHODS: A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure-pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1-2 versus 3-4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30). RESULTS: Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain-sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race. CONCLUSION: The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate-to-severe radiographic evidence of pathologic changes of knee OA.

Association of vitamin D with cardiometabolic risk factors in rheumatoid arthritis.

OBJECTIVE: Individuals with rheumatoid arthritis (RA) are at a greater risk for cardiovascular disease (CVD). Vitamin D deficiency is a potential risk factor for CVD and metabolic syndrome. Since patients with RA have a high prevalence of vitamin D deficiency, we investigated the association of vitamin D levels with cardiometabolic risk factors in a cohort of RA patients with no prior history of CVD. METHODS: Serum 25-hydroxyvitamin D (25[OH]D) levels were measured among RA patients enrolled in a cohort study of subclinical CVD. The cross-sectional associations of 25(OH)D levels with traditional CVD risk factors such as insulin resistance (IR; estimated using the homeostatic model assessment [HOMA]), adipokines, markers of systemic inflammation, and endothelial activation were explored, adjusting for pertinent sociodemographic, lifestyle, and RA characteristics. RESULTS: Among 179 RA patients, 73 (41%) had a 25(OH)D level <30 ng/ml. Only 23 patients (13%) had a 25(OH)D level ≥45 ng/ml. After adjusting for demographics and body mass index (BMI), 25(OH)D remained significantly associated with high-density lipoprotein (HDL) cholesterol and inversely associated with HOMA-IR, fibrinogen, E-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1). Significant associations with HDL cholesterol, E-selectin, and sICAM-1 were maintained after adjusting for the Disease Activity Score in 28 joints (DAS28) and autoantibody status. These associations were similar between the groups subdivided by sex, ethnicity, BMI, DAS28 level, and autoantibody status. CONCLUSION: These data suggest that vitamin D deficiency is common in RA and may be independently associated with several cardiometabolic intermediates in this population.

Recurrent Kawasaki disease with strawberry tongue and skin desquamation in a young adult.

A 19-year-old man with history of Kawasaki disease (KD) at age 12 developed intractable fevers, swelling in hands and feet, arthralgias, and conjunctivitis, followed by strawberry tongue and desquamation of distal extremities. Laboratory studies revealed leukocytosis, thrombocytosis, anemia, elevated erythrocyte sedimentation rate and C-reactive protein levels, and mildly elevated liver enzymes. He was empirically treated with broad-spectrum antibiotics without any improvement. Extensive infectious and rheumatologic workup remained negative. Recurrence of KD was diagnosed based on characteristic mucocutaneous changes and systemic inflammatory response. His symptoms and laboratory values responded rapidly to intravenous immunoglobulin and aspirin therapy. An echocardiogram did not show any coronary abnormality. We report the third case of pediatric KD relapsing in adulthood. Similar to childhood and adult KD, these recurrent episodes respond well to intravenous immunoglobulin therapy. Although recurrent KD is rare, our case highlights the importance of considering it in the differential of febrile illness in the appropriate individual.

Rheumatoid arthritis and reproduction.

Additional research is needed to establish the safety of biologic agents in pregnancy and lactation. The practitioner should convey information regarding the natural history of rheumatoid arthritis during pregnancy and safety issues related to pharmacotherapies to every woman of childbearing age with RA, well before conception and pregnancy, to ensure optimal outcomes.

The role of biologicals in early rheumatoid arthritis.

Recent emphasis on early diagnosis and treatment of rheumatoid arthritis (RA) to improve long-term disease outcome has raised important questions about optimal therapy for early RA. With an expanding armamentarium of disease-modifying antirheumatic drugs including biological agents, there are now several therapeutic choices available to clinicians. However, at early stages of arthritis, difficulty in accurately predicting individual prognosis and response to therapy continues to pose a significant challenge. Future research in biomarkers of progressive, erosive disease and controlled trials to establish the most effective therapies in early RA will greatly enhance our ability to minimize the impact of this potentially disabling disease.