Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies.

OBJECTIVES: This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA). METHODS: This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs). RESULTS: ~49 000 patients receiving abatacept were analysed from clinical trials (~7000) and observational studies (~42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2-30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2-130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5-12 (abatacept), 1.6-10 (csDMARDs) and 3-8 (other b/tsDMARDs). Claims database IRs were 19-22 (abatacept), 15-18 (csDMARDs) and 14-17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs. CONCLUSIONS: Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity.

Major adverse cardiovascular events and mortality with opioids versus NSAIDs initiation in patients with rheumatoid arthritis.

OBJECTIVE: Assess major adverse cardiovascular event (MACE) risk with opioids compared with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) METHODS: We conducted a new-user active comparator cohort study among patients with RA within FORWARD, The National Databank for Rheumatic Diseases, with ≥1 year participation between 1998 and 2021. Each opioid initiator was matched to two NSAID initiators by propensity scores (PSs). Patients were followed until the occurrence of the composite endpoint of MACE (myocardial infarction, stroke, heart failure, cardiovascular disease (CVD) death, venous thromboembolism (VTE)) and all-cause mortality. The risk of outcomes was estimated using Cox proportional hazards with adjustment for PS weights and imbalanced covariables. RESULTS: Among 6866 opioid initiators and 13 689 NSAID initiators, 212 vs 253 MACE (20.6/1000 person-years (PY) vs 18.9/1000 PY) and 144 vs 150 deaths (13.5/1000 PY vs 10.8/1000 PY) occurred, respectively. The risk of MACE with opioids was similar to NSAIDs (HR=1.02, 95% CI 0.85 to 1.22), whereas all-cause mortality with opioids was 33% higher than NSAIDs (HR=1.33, 95% CI 1.06 to 1.67) in PS-weighted models. Among the individual outcomes of MACE, VTE risk tended to be higher in opioid initiators than NSAID initiators (HR=1.41, 95% CI 0.84 to 2.35). Strong opioids had a higher risk for all-cause mortality and VTE than weak opioids compared with NSAIDs suggesting a dose-dependent association. CONCLUSION: Opioids had similar MACE risk compared with NSAIDs in patients with RA with increased all-cause mortality and likely VTE, which suggests that opioids are not safer than NSAIDs, as clinicians have perceived.

Smartphone-based behavioral monitoring and patient-reported outcomes in adults with rheumatic and musculoskeletal disease.

BACKGROUND: Rheumatic and musculoskeletal diseases (RMD) are associated with depression, fatigue, and disturbed sleep - symptoms that often impact behavior and activity. Patient reported outcomes (PROs) are a way of collecting information on the patient symptom experience directly from the individual. The purpose of this study was to measure and compare user smartphone sensor and activity data in adults with RMDs and assess associations with PROs. METHODS: We invited adults with RMDs enrolled in the FORWARD Databank to participate by installing a custom app on their smartphone and answering PROs (pain, global, HAQ-II) questions daily and weekly over 3 years. Passive data collected included mobility distance, unique calls and text messages, call durations, and number of missed calls. Confounders included sociodemographic, clinical, passive phone behavior, and seasonal factors. Kappa statistics between PRO and flares were computed to measure agreement. The agreement between daily and weekly VAS pain was estimated using the intraclass (ICC) correlation of a two-way random effect model. The relationship between the weekly PRO outcomes and the passive phone data was analyzed with a linear mixed-effect model (LMM), including a random intercept for participant and slope for time in the study with an unstructured covariate structure. RESULTS: Of the 446 participants, the mean (SD) age was 54 (12) years, most (65.5%) had rheumatoid arthritis (RA), the vast majority (91%) were female, and the US Northeast has the least representation (12%). Longer reaction times, interaction diversity, and higher mobility were associated with worse PROs while longer text messages were associated with better PROs. Participants in this study showed good levels of adherence which holds promise for future interventions using passive behavior measures in self-management and clinical follow-up. CONCLUSION: This is the first study to examine passive smartphone behavior with PROs in RMDs and we found significant associations between these behaviors and important health outcomes of pain and function. As smartphone usage continues to change, future studies should validate and expand on our findings with a goal of finding changes in patient symptoms passively through mobile device monitoring.

The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial.

BACKGROUND: The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). OBJECTIVE: To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. DESIGN: Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). SETTING: Academic and community-based rheumatology, gastroenterology, and dermatology practices. PATIENTS: Adults aged 50 years or older receiving TNFis for any indication. INTERVENTION: Random assignment to ZVL versus placebo. MEASUREMENTS: Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. RESULTS: Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. LIMITATION: Potentially limited generalizability to patients receiving other types of immunomodulators. CONCLUSION: This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. PRIMARY FUNDING SOURCE: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). METHODS: We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. RESULTS: This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. CONCLUSION: This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

Burden and trajectory of multimorbidity in rheumatoid arthritis: a matched cohort study from 2006 to 2015.

OBJECTIVES: To compare the onset and trajectory of multimorbidity between individuals with and without rheumatoid arthritis (RA). METHODS: A matched, retrospective cohort study was completed in a large, US commercial insurance database (MarketScan) from 2006 to 2015. Using validated algorithms, patients with RA (overall and incident) were age-matched and sex-matched to patients without RA. Diagnostic codes for 44 preidentified chronic conditions were selected to determine the presence (≥2 conditions) and burden (count) of multimorbidity. Cross-sectional comparisons were completed using the overall RA cohort and conditional logistic and negative binomial regression models. Trajectories of multimorbidity were assessed within the incident RA subcohort using generalised estimating equations. RESULTS: The overall cohort (n=277 782) and incident subcohort (n=61 124) were female predominant (76.5%, 74.1%) with a mean age of 55.6 years and 54.5 years, respectively. The cross-sectional prevalence (OR 2.29, 95% CI 2.25 to 2.34) and burden (ratio of conditions 1.68, 95% CI 1.66 to 1.70) of multimorbidity were significantly higher in RA than non-RA in the overall cohort. Within the incident RA cohort, patients with RA had more chronic conditions than non-RA (ß 1.13, 95% CI 1.10 to 1.17), and the rate of accruing chronic conditions was significantly higher in RA compared with non-RA (RA × follow-up year, ß 0.21, 95% CI 0.20 to 0.21, p<0.001). Results were similar when including the pre-RA period and in several sensitivity analyses. CONCLUSIONS: Multimorbidity is highly prevalent in RA and progresses more rapidly in patients with RA than in patients without RA during and immediately following RA onset. Therefore, multimorbidity should be aggressively identified and targeted early in the RA disease course.

Applying SLICC and ACR/EULAR systemic lupus erythematosus classification criteria in a cohort of patients with undifferentiated connective tissue disease.

BACKGROUND/OBJECTIVE: New classification criteria for SLE have recently been developed. How these criteria affect the classification of patients with the SLE-mimicking condition UCTD is poorly understood. This study investigated the reclassification of UCTD patients using newly derived SLE criteria. METHODS: Patients with UCTD were identified within a single academic medical center using ICD9/10 codes. Medical record review was performed to confirm UCTD diagnosis and identify disease features present at diagnosis. The SLICC and ACR/EULAR criteria were applied, after which we compared the proportion of patients reclassified as SLE and determined which disease features were associated with reclassification. RESULTS: A total of 129 patients were included in the study. When applying the SLICC and ACR/EULAR criteria, 18 (14.0%) and 26 patients (20.2%) were reclassified as SLE. Comparison with McNemar's test trended toward statistical significance (p = 0.057). Cohen's kappa coefficient was 0.62 (p < 0.001), indicating substantial agreement between these criteria. Disease features associated with reclassification as SLE were renal involvement, leukopenia, thrombocytopenia, anti- dsDNA antibody, hypocomplementemia, non-scarring alopecia (SLICC), and arthritis (ACR/EULAR). CONCLUSIONS: Both the SLICC and ACR/EULAR criteria exhibit increased SLE classification. These newer classification criteria could be used to increase the number of SLE patients in future clinical studies.

Effects of the SARS-CoV-2 global pandemic on U.S. rheumatology outpatient care delivery and use of telemedicine: an analysis of data from the RISE registry.

The SARS-CoV-2 global pandemic resulted in major disruptions to medical care. We aimed to understand changes in outpatient care delivery and use of telemedicine in U.S. rheumatology practices during this period. Rheumatology Informatics System Effectiveness (RISE) is a national, EHR-enabled registry that passively collects data on all patients seen by participating practices. Included practices were required to have been participating in RISE from January 2019 through August 2020 (N = 213). We compared total visit counts and telemedicine visits during March-August 2020 to March-August 2019 and stratified by locations in states with shelter-in-place (SIP) orders. We assessed characteristics of patients within each practice, including primary rheumatic diagnosis and disease activity scores, where available. We included 213 practices with 945,160 patients. Overall, we found visit counts decreased by 10.9% (from 1,302,455 to 1,161,051) between March and August 2020 compared to 2019; this drop was most dramatic during the month of April (- 22.3%). Telemedicine visits increased from 0% to a mean of 12.1%. Practices in SIP states had more dramatic decreases in visits, (11.5% vs. 5.3%). We found no major differences in primary diagnoses or disease activity across the two periods. We detected a meaningful decrease in rheumatology visits in March-August 2020 during the SARS-CoV-2 global pandemic compared to the year prior with a concomitant increase in the use of telemedicine. Future work should address possible adverse consequences to patient outcomes due to decreased contact with clinicians.

Self-Management of Rheumatoid Arthritis: Mobile Applications.

PURPOSE OF REVIEW: To review the self-management of rheumatoid arthritis (RA) using mobile applications. RECENT FINDINGS: Recent research supports that self-management not only can be an empowering behavior for an individual but also has been shown to improve health outcomes in RA. Mobile health applications are growing in popularity and adoption. Emerging evidence supports that using a mobile application for RA self-management may reduce disease activity and improve health outcomes. This review discusses mobile applications designed to improve self-management of RA as well as applications not specific to RA that also may be useful for self-management in this population. Future research should focus on the efficacy of mobile apps for health outcomes and ways to improve the adoption of and adherence to mobile apps in individuals with RA.

Medications associated with fracture risk in patients with rheumatoid arthritis.

OBJECTIVE: To examine the fracture risk with use of disease-modifying antirheumatic drugs (DMARDs), statins, proton pump inhibitors (PPIs), opioids, non-opioid analgesics and psychotropic medications in a US-wide observational rheumatoid arthritis (RA) cohort. METHODS: Patients with RA without prior fracture from 2001 through 2017 in FORWARD, a longitudinal observational registry, were assessed for osteoporosis-related site fractures (vertebra, hip, forearm and humerus). DMARD exposure was assessed in four mutually exclusive groups: (1) methotrexate monotherapy-reference, (2) tumour necrosis factor-α inhibitors (TNFi), (3) non-TNFi biologics and (4) others. Non-DMARDs and glucocorticoids were classified as current/ever use and based on treatment duration. Fracture Risk Assessment Tool (FRAX) scores estimating for 10-year major osteoporotic fractures were calculated. Cox proportional hazard models stratified by FRAX were used to adjust for confounders. RESULTS: During median (IQR) 3.0 (1.5-6.0) years of follow-up in 11 412 patients, 914 fractures were observed. The adjusted models showed a significant fracture risk increase with use of any dose glucocorticoids ≥3 months (HR (95% CI) for <7.5 mg/day 1.26 (1.07 to 1.48) and for ≥7.5 mg/day 1.57 (1.27 to 1.94)), opioids (for weak: 1.37 (1.18 to 1.59); strong: 1.53 (1.24 to 1.88)) and selective serotonin reuptake inhibitors (SSRIs) (1.37 (1.15 to 1.63)). Fracture risk with opioids increased within 1 month of use (1.66 (1.36 to 2.04)) and with SSRIs >3 months of use (1.25 (1.01 to 1.55)). Statins (0.77 (0.62 to 0.96)) and TNFi (0.72 (0.54 to 0.97)) were associated with reduction in vertebral fracture risk only. PPIs and other psychotropic medications were not associated with increased fracture risk. CONCLUSION: Use of opioids, SSRIs and glucocorticoids were associated with increased risk of any fracture in patients with RA, whereas statins and TNFi were associated with decreased vertebral fractures.

Current and early life weight and associations with mortality in rheumatoid arthritis.

OBJECTIVES: Obesity is paradoxically associated with a lower risk of mortality in chronic illnesses including rheumatoid arthritis (RA). Weight loss in patients with poor health, however, may in part explain this observation. This study evaluated the impact of weight early in life and weight loss on mortality in patients with RA. METHODS: Patients with RA (age >40 years) were active participants in a prospective clinical registry with up to 17 years of follow-up. Current and age-30 body mass index (BMI) were determined from self-report of height and weight from semi-annual questionnaires. Mortality was assessed from National Death Index. Risks of obesity reported from both early in life and at enrolment in the registry were evaluated using Cox proportional hazards models. RESULTS: Among 12,679 participants (80% female), there were 1,520 deaths in 80,502 person-years. Obesity at enrolment (BMI >30 kg/m2) was modestly associated with greater mortality [HR: 1.34 (1.18,1.53) p=0.001]. Adjusting for disability and comorbidities hypothesised to be mediators in the causal pathway between obesity and mortality further attenuated this association [HR: 0.92 (0.80,1.06) p=0.24]. In contrast, obesity at age 30 was strongly associated with mortality [HR: 2.00 (1.65,2.42) p<0.001]. Additionally, weight loss since age-30 was a strong, dose-dependent predictor of mortality independent of enrolment BMI. CONCLUSIONS: The risk of obesity is substantially underestimated when epidemiologic methods do not account for long-term weight changes. Both obesity and weight loss are strongly associated with mortality risk in patients with RA.

Using technology to support clinical care and research in rheumatoid arthritis.

PURPOSE OF REVIEW: As digital technology becomes more ubiquitous, understanding the current state-of-the-art in digital information use for clinical care and research for patients with rheumatoid arthritis (RA) is timely and relevant. RECENT FINDINGS: The opportunities for recording and utilizing high-quality data from rheumatologists are reviewed, as well as opportunities from collecting, integrating and analysing patient-generated data to deliver a step-change in the support and management of RA. SUMMARY: Once greater adoption, standardization and implementation of relevant RA measures are in place within electronic health records (EHRs), patient care will improve and the ability to learn from aggregate experiences increases dramatically. Incorporating passive and patient-reported outcomes into self-management apps and integrating such data into the patient's health record will provide more responsive and better treatment results.

The impact of menopause on functional status in women with rheumatoid arthritis.

Objective: The aim of this study was to investigate the association of menopause with functional status outcomes in women with RA. Methods: Participants were women in a US-wide observational cohort who developed RA before menopause. The HAQ measured functional status. We controlled for confounding variables and used univariate and multivariable generalized estimating equation methods with the sandwich estimator of variance. Best models were selected using the quasi-likelihood under the independence model criterion. A sensitivity analysis was performed using linear mixed effects regression models. Results: A total of 8189 women were eligible. Of these, 2005 (24.5%) were pre-menopausal, 611 (7.5%) transitioned through menopause during the study, and 5573 (68.1%) were post-menopausal. Within each respective group, the mean (s.d.) ages were 39.7 (7.8), 50.7 (3.4) and 62.3 (9.3) years. Our results showed that women who were pre-menopausal had less functional decline as measured by the HAQ compared with women who were post-menopausal; these results were robust and strong even after adjustment for other significant factors. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. After menopause, the trajectory of functional decline worsened and accelerated in women with RA. Conclusion: The results suggest that menopausal status is associated with functional decline in women with RA. Furthermore, menopause is associated with a worsening progression of functional decline. These data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.

Deriving common comorbidity indices from the MedDRA classification and exploring their performance on key outcomes in patients with rheumatoid arthritis.

OBJECTIVE: To develop algorithms for calculating the Rheumatic Diseases Comorbidity Index (RDCI), Charlson-Deyo Index (CDI) and Functional Comorbidity Index (FCI) from the Medical Dictionary for Regulatory Activities (MedDRA), and to assess how these MedDRA-derived indices predict clinical outcomes, utility and health resource utilization (HRU). METHODS: Two independent researchers linked the preferred terms of the MedDRA classification into the conditions included in the RDCI, the CDI and the FCI. Next, using data from the Norwegian Register-DMARD study (a register of patients with inflammatory joint diseases treated with DMARDs), the explanatory value of these indices was studied in models adjusted for age, gender and DAS28. Model fit statistics were compared in generalized estimating equation (prediction of outcome over time) models using as outcomes: modified HAQ, HAQ, physical and mental component summary of SF-36, SF6D and non-RA related HRU. RESULTS: Among 4126 patients with RA [72% female, mean (s.d.) age 56 (14) years], median (interquartile range) of RDCI at baseline was 0.0 (1.0) [range 0-6], CDI 0.0 (0.0) [0-7] and FCI 0.0 (1.0) [0-6]. All the comorbidity indices were associated with each outcome, and differences in their performance were moderate. The RDCI and FCI performed better on clinical outcomes: modified HAQ and HAQ, hospitalization, physical and mental component summary, and SF6D. Any non-RA related HRU was best predicted by RDCI followed by CDI. CONCLUSION: An algorithm is now available to compute three commonly used comorbidity indices from MedDRA classification. Indices performed comparably well in predicting a variety of outcomes, with the CDI performing slightly worse when predicting outcomes reflecting functioning and health.

Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis Is Associated With Changes in Blood Pressure.

PURPOSE: This study reports the effect of disease-modifying therapies for rheumatoid arthritis (RA) on systolic and diastolic blood pressure (SBP, DBP) over 6 months and incident hypertension over 3 years in a large administrative database. METHODS: We used administrative Veterans Affairs databases to define unique dispensing episodes of methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, tumor necrosis factor inhibitors, and prednisone among patients with RA. Changes in SBP and DBP in the 6 months before disease-modifying antirheumatic drug initiation were compared with changes observed in the 6 months after initiation. The risk of incident hypertension within 3 years (new diagnosis code for hypertension and prescription for antihypertensive) was also assessed. Multivariable models and propensity analyses assessed the impact of confounding by indication. RESULTS: A total of 37,900 treatment courses in 21,216 unique patients contributed data. Overall, there were no changes in SBP or DBP in 6 months prior to disease-modifying antirheumatic drug initiation (all P > 0.62). In contrast, there was a decline in SBP (ß = -1.08 [-1.32 to -0.85]; P < 0.0001) and DBP (ß = -0.48 [-0.62 to -0.33]; P < 0.0001) over the 6 months following initiation. The greatest decline was observed among methotrexate and hydroxychloroquine users. Methotrexate users were 9% more likely to have optimal blood pressure (BP) after 6 months of treatment. Patients treated with leflunomide had increases in BP and a greater risk of incident hypertension compared with patients treated with methotrexate (hazard ratio, 1.53 [1.21-1.91]; P < 0.001). CONCLUSIONS: Blood pressure may improve with treatment of RA, particularly with methotrexate or hydroxychloroquine. Leflunomide use, in contrast, is associated with increases in BP and a greater risk of incident hypertension.

Risk of diabetes mellitus associated with disease-modifying antirheumatic drugs and statins in rheumatoid arthritis.

OBJECTIVE: To investigate the rate of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) and the impact of disease-modifying antirheumatic drug (DMARD) and statin treatments. METHODS: We studied patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases without baseline DM from 2000 through 2014. DM was determined by self-report or initiating DM medication. DMARDs were categorised into four mutually exclusive groups: (1) methotrexate monotherapy (reference); (2) any abatacept with or without synthetic DMARDs (3) any other DMARDs with methotrexate; (4) all other DMARDs without methotrexate; along with separate statin, glucocorticoid and hydroxychloroquine (yes/no) variables. Time-varying Cox proportional hazard models were used to adjust for age, sex, socioeconomic status, comorbidities, body mass index and RA severity measures. RESULTS: During a median (IQR) 4.6 (2.5-8.8) years of follow-up in 13 669 patients with RA, 1139 incident DM cases were observed. The standardised incidence ratio (95% CI) of DM in patients with RA (1.37, (1.29 to 1.45)) was increased compared with US adult population. Adjusted HR (95% CI) for DM were 0.67 (0.57 to 0.80) for hydroxychloroquine, 0.52 (0.31 to 0.89) for abatacept (compared with methotrexate monotherapy), 1.31 (1.15 to 1.49) for glucocorticoids and 1.56 (1.36 to 1.78) for statins. Other synthetic/biological DMARDs were not associated with any risk change. Concomitant use of glucocorticoids did not alter DM risk reduction with hydroxychloroquine (HR 0.69 (0.51 to 0.93)). CONCLUSIONS: In RA, incidence of DM is increased. Hydroxychloroquine and abatacept were associated with decreased risk of DM, and glucocorticoids and statins with increased risk.

Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint.

Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry. Results: Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01). Conclusion: Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.

Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014.

This study aimed to determine the prevalence of rheumatoid arthritis in the United States (US) adult insured population from 2004 to 2014. This was an observational, retrospective, cross-sectional study based on US administrative health insurance claims databases (Truven Health MarketScan® Research database and IMS PharMetrics Plus database). Trends in RA prevalence focusing on the 10-year period covering January 1, 2004-December 31, 2014 were analyzed using a validated algorithm for the identification of RA. Prevalence rates in the databases were determined and age- and gender-adjusted rates were projected to the US population in 2014. Analysis of data from the two databases indicated that the RA prevalence rate in commercially insured adult US population ranged from 0.41 to 0.54% from 2004 to 2014. The prevalence varied substantially by gender and age in each year and increased gradually across the years for most subgroups. In 2014, out of 31,316,902 adult patients with continuous enrollment in the Truven Health MarketScan® Research database, 157,634 (0.50%) patients met our criteria for RA. Similarly, out of 35,083,356 adult patients in the IMS PharMetrics Plus database, 139,300 (0.50%) patients met our criteria for RA. In 2014, the overall age-adjusted prevalence of RA ranged from 0.53 to 0.55% (0.29-0.31% for males and 0.73-0.78% for females). The prevalence of RA in the US appeared to increase during the period from 2004 to 2014, affecting a conservative estimate of 1.28-1.36 million adults in 2014.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

OBJECTIVE: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). METHODS: A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. RESULTS: The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low- or moderate-quality evidence. CONCLUSION: This guideline should help decision-making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high-quality direct randomized controlled trial data.