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Objective: To provide evidence‐based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). Methods: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. Results: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. Conclusion: Application of these recommendations should consider patients' individual risk for vaccine‐preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision‐making with patients is encouraged in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Pain sensitization may contribute to pain severity in rheumatoid arthritis (RA), impacting disease activity assessment. We examined whether pain processing mechanisms were associated with disease activity among RA patients with active disease.Methods: The study included 139 subjects enrolled in the Central Pain in Rheumatoid Arthritis cohort. Subjects underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at multiple sites, conditioned pain modulation, and temporal summation. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI) and its components. We examined cross-sectional associations between QST measures and disease activity using linear regression.Results: Low PPTs (high pain sensitization) at all sites were associated with high CDAI scores (P ≤ 0.03) and tender joint counts (P ≤ 0.002). Associations between PPTs and patient global assessments were also seen at most sites. High temporal summation at the forearm (also reflecting high pain sensitization) was significantly associated with high CDAI scores (P = 0.02), patient global assessment scores (P = 0.0006), evaluator global assessment scores (P = 0.01), and tender joint counts (P = 0.02). Conversely, conditioned pain modulation (a measure of descending inhibitory pain pathways) was associated only with tender joint count (P = 0.03).Conclusion: High pain sensitization is associated with elevations in disease activity measures. Longitudinal studies are underway to elucidate the cause-effect relationships between pain sensitization and inflammatory disease activity in RA. [ABSTRACT FROM AUTHOR]

Objective: To assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28-2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT-RAY study.Methods: Patients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28-2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28-2 definition.Results: After tocilizumab discontinuation, DAS28-2 was sensitive (88-100%), but not specific (57-65%), for detecting investigator flare. Under constant treatment, DAS28-2 criteria were met in 136 cases per 100 patient-years despite stable disease activity. Sustained flares were infrequent. Other DAS28-based criteria led to similar conclusions.Conclusion: DAS28-based flare occurred more often than investigator-defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs)., Methods: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation., Results: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence., Conclusion: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings., (© 2023 American College of Rheumatology.)

Background/objectives: We hypothesized that emotional distress in systemic sclerosis (SSc) patients with moderate to severe gastrointestinal (GI) dysfunction is associated with dysautonomia. We sought to determine (1) the clinical characteristics associated with emotional distress in SSc, (2) the odds of having dysautonomia in those with emotional distress, and (3) whether GI dysautonomia, as measured by the Survey of Autonomic Symptoms (SAS), correlates with GI dysautonomia on the Composite Autonomic Symptom Score-31 (COMPASS-31)., Methods: Clinical and demographic features from our prospective cohort study were compared among SSc patients with and without GI-associated emotional distress (University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 well-being subscale >0.5 or ≤0.5) in cross-sectional analysis. Covariates/confounders independently associated with emotional distress were used to construct multivariable logistic regression models. The COMPASS-31 and SAS GI subdomains were compared with Spearman correlation., Results: Forty-six patients with SSc were enrolled in the study. In univariate analyses, age (odds ratio [OR], 1.06; p = 0.026), severity of GI dysautonomia (COMPASS-31: OR, 1.41; p = 0.003), anti-centromere (A/B) antibodies (OR, 3.60; p = 0.044), and anti-PM-Scl (75/100) antibodies (OR, 0.15; p = 0.035) were associated with emotional distress. In the adjusted model, those with more severe GI dysautonomia remained more likely to have emotional distress (OR, 1.85; p = 0.026); those with anti-PM-Scl (75/100) antibodies were less likely to have emotional distress (OR, 0.03; p = 0.031). The SAS and COMPASS-31 GI subdomains moderately correlated (ρ = 0.68, p < 0.001)., Conclusions: In SSc, increased symptom burden related to GI dysautonomia is associated with emotional distress. Multidisciplinary approaches addressing both the physical and emotional needs of the SSc patient may be warranted to optimize patient care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting., Methods: Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%., Results: Participants in ODB were 53 patients with JIA (ages 15-24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient's perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories., Conclusion: Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections., Methods: Using the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with ( n = 17) and those without infections ( n = 6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays., Results: We identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections., Conclusions: Our study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.

Introduction: Previous research suggests patients with rheumatoid arthritis (RA) may receive suboptimal care with respect to preventive tests and services. We evaluated the proportion of older Americans with RA, psoriatic arthritis (PsA), and osteoarthritis (OA) receiving these services and the specialty of the providers delivering this care., Methods: Using data from 1999 to 2006 from the Medicare Chronic Conditions Warehouse, we identified persons age >/= 65 in the national 5% sample. Over the required five-year observation period, we identified tests and services recommended for older adults and the associated healthcare provider. Services of interest included dual energy x-ray absorptiometry (DXA), influenza and pneumococcal vaccination, hyperlipidemia lab testing, mammography and colonoscopy., Results: After accounting for the sampling fraction, we identified 141,140 RA, 6,300 PsA, and 770,520 OA patients eligible for analysis. Over five years, a majority of RA, PsA, and OA patients were tested for hyperlipidemia (84%, 89% and 87% respectively) and received DXA (69%, 75%, and 52%). Only approximately one-third of arthritis patients received pneumococcal vaccination; 19% to 22% received influenza vaccination each year. Approximately 20% to 35% of arthritis patients never underwent mammography and colonoscopy over five years. Concomitant care from both a rheumatologist and a primary care physician was significantly associated with a greater likelihood of receiving almost all preventive tests and services., Conclusions: Among older Americans on Medicare, the absolute proportion of persons with arthritis receiving various recommended preventive services and screening tests was substantially less than 100%. Improved co-management between primary care and arthritis physicians may in part improve the delivery of preventive care for arthritis patients, but novel systematic interventions in this area are needed.

Objective: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders., Methods: After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop., Results: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful., Conclusion: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.