Malignancy outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate the risk of malignancy (overall, breast, lung, and lymphoma) in patients with rheumatoid arthritis treated with abatacept, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), and other biologic/targeted synthetic (b/ts)DMARDs in clinical practice. METHODS: Four international observational data sources were included: ARTIS (Sweden), RABBIT (Germany), FORWARD (USA), and BC (Canada). Crude incidence rates (IRs) per 1000 patient-years of exposure with 95% confidence intervals (CIs) for a malignancy event were calculated; rate ratios (RRs) were estimated and adjusted for demographics, comorbidities, and other potential confounders. RRs were then pooled in a random-effects model. RESULTS: Across data sources, mean follow-up for patients treated with abatacept (n = 5182), csDMARDs (n = 73,755), and other b/tsDMARDs (n = 37,195) was 3.0-3.7, 2.9-6.2, and 3.1-4.7 years, respectively. IRs per 1000 patient-years for overall malignancy ranged from 7.6-11.4 (abatacept), 8.6-13.2 (csDMARDs), and 5.0-11.8 (other b/tsDMARDs). IRs ranged from: 0-4.4, 0-3.3, and 0-2.5 (breast cancer); 0.1-2.8, 0-3.7, and 0.2-2.9 (lung cancer); and 0-1.1, 0-0.9, and 0-0.6 (lymphoma), respectively, for the three treatment groups. The numbers of individual cancers (breast, lung, and lymphoma) in some registries were low; RRs were not available. There were a few cases of lymphoma in some of the registries; ARTIS observed an RR of 2.8 (95% CI 1.1-6.8) with abatacept versus csDMARDs. The pooled RRs (95% CIs) for overall malignancy with abatacept were 1.1 (0.8-1.5) versus csDMARDs and 1.0 (0.8-1.3) versus b/tsDMARDs. CONCLUSIONS: This international, post-marketing observational safety study did not find any statistically significant increase in the risk of overall malignancies in pooled data in patients treated with abatacept compared with csDMARDs or with other b/tsDMARDs. Assessment of larger populations is needed to further evaluate the risks for individual cancers, especially lymphoma.

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study.

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Treatment Adherence and Adherence Patterns of Tofacitinib and Self-Injectable TNFi Use in People with Rheumatoid Arthritis.

OBJECTIVE: To assess tofacitinib and self-injectable tumor necrosis factor inhibitor (TNFi) adherence using the Medication Event Monitoring System (MEMS) and characterize association with adherence in patients with rheumatoid arthritis (RA). METHODS: Eligible patients were enrolled from the Forward Databank within 6 months of initiating tofacitinib or injectable TNFi or from participating clinics where these were first prescribed. MEMS caps and patient diaries were used to compile dosing over 9 months. Demographics and disease characteristics were collected every 6 months, and the Beliefs about Medicines Questionnaire only at baseline. Adherence along with its components, initiation, implementation, and persistence, were calculated. RESULTS: Of the 112 consented to participate, 82 (73%) remained in the final analysis with recruitment from clinics 47 (57%) and Forward 35 (43%). Sixty-two (76%) initiated tofacitinib with 87% taking it quaque die and twenty (24%) TNFi. At 9 months, 77% of tofacitinib were persistent versus 70% for TNFi (P = 0.65), and implementation was similar (0.84 vs. 0.82; P = 0.57). In multivariable models, increased baseline patient global assessment was consistently associated with discontinuation (hazard ratio 1.31 [1.07-1.61]). There was increased adherence to methotrexate (MTX) when taking tofacitinib that led to higher combined adherence for tofacitinib than TNFi (0.81 vs. 0.69; P = 0.03), but no significant differences remained in multivariable models. In sensitivity analysis, consistent morning intake for tofacitinib and evening intake for MTX was associated with improved adherence. CONCLUSION: We found no statistical differences in adherence between patients with RA initiating tofacitinib and self-injectable TNFi, although 15% to 30% were nonadherent. Concomitant MTX, patient global assessment, and a consistent time of day intake were associated with adherence.

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.

Comparative effectiveness of treatments for rheumatoid arthritis in clinical practice: A systematic review.

OBJECTIVE: To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA) through a systematic review. METHODS: We searched Medline for journal articles (2001-2021) and Embase® for abstracts presented at the European Alliance of Associations for Rheumatology and American College of Rheumatology (ACR) 2020 and 2021 annual meetings on non-randomized studies comparing the effectiveness of b/tsDMARDs using ACR-recommended disease activity measures, measures of functional status, and patient-reported outcomes (HAQ, PROMIS PF, patient pain, Patient and Physician Global Assessment of disease activity). Methodological heterogeneity between studies precluded meta-analyses. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions-I tool. RESULTS: Of 1283 records screened, 68 were selected for data extraction, of which 1 was excluded due to critical risk of bias. Most studies were multicenter observational cohort/registry studies (n = 60) and were published between 2011 and 2021 (n = 60). Mean or median reported RA duration was between 6 and 15 years. Disease Activity Score in 28 joints (46 studies), Clinical Disease Activity Index (37 studies), and Health Assessment Questionnaire-Disability Index (32 studies) were the most common outcomes used in clinical practice, with regional differences identified. The most common comparison was between tumor necrosis factor inhibitors (TNFis) and non-TNFi bDMARDs (35 studies). There were no evident differences between b/tsDMARDs in clinical effectiveness. CONCLUSION: This systematic review summarizing real-world evidence from a very large number of global studies found there are many effective options for the treatment of RA, but relatively less evidence to support the use of any one b/tsDMARD or drug class over another. Treatment for patients with RA should be tailored to suit individual clinical profiles. Further research is needed to identify whether specific patient subgroups may benefit from specific drug classes.

Multimorbidity Patterns and Rheumatoid Arthritis Disease Outcomes: Findings From a Multicenter, Prospective Cohort.

OBJECTIVE: To determine whether unique multimorbidity patterns are associated with long-term rheumatoid arthritis (RA) disease severity. METHODS: We conducted a cohort study within the Veterans Affairs Rheumatoid Arthritis registry. We applied previously derived multimorbidity patterns based on the presence of diagnostic codes for relevant conditions prior to enrollment using linked administrative data. Disease activity and functional status were assessed longitudinally up to 5 years after enrollment. The association of multimorbidity patterns with disease activity and functional status were assessed using generalized estimating equations models adjusting for relevant confounders. RESULTS: We studied 2,956 participants, of which 88.2% were male, 76.9% reported white race, and 79.3% had a smoking history. Mental health and substance abuse (ß 0.12 [95% confidence interval {CI} 0.00, 0.23]), cardiovascular (ß 0.25 [95% CI 0.12, 0.38]), and chronic pain (ß 0.21 [95% CI 0.11, 0.31]) multimorbidity were associated with higher Disease Activity Score in 28 joints (DAS28) scores. Mental health and substance abuse (ß 0.09 [0.03, 0.15]), cardiovascular (ß 0.11 [95% CI 0.04, 0.17]), and chronic pain multimorbidity (ß 0.15 [95% CI 0.10, 0.20]) were also associated with higher Multidimensional Health Assessment Questionnaire (MDHAQ) scores. The metabolic pattern of multimorbidity was not associated with DAS28 or MDHAQ. The number of multimorbidity patterns present was highly associated with DAS28 and MDHAQ (P trend < 0.001), and patients with all four multimorbidity patterns had the highest DAS28 (ß 0.59 [95% CI 0.36, 0.83]) and MDHAQ (ß 0.27 [95% CI 0.16, 0.39]) scores. CONCLUSION: Mental health and substance abuse, chronic pain, and cardiovascular multimorbidity patterns are associated with increased RA disease activity and poorer functional status. Identifying and addressing these multimorbidity patterns may facilitate achieving RA treatment targets.

Urban and Rural Patterns of Health Care Utilization Among People With Rheumatoid Arthritis and Osteoarthritis in a Large US Patient Registry.

OBJECTIVE: Rural residence has been associated with health disparities in rheumatic diseases and other chronic conditions in the United States. This study aimed to determine if a relationship exists between geographic residence and health care utilization outcomes for people with rheumatoid arthritis (RA) and osteoarthritis (OA) in a US-wide rheumatic disease registry. METHODS: Participants were in FORWARD, The National Databank for Rheumatic Diseases, a US-wide rheumatic disease longitudinal cohort completing questionnaires between 1999 and 2019. Health care utilization variables (ie, medical visits and diagnostic tests) from six-month questionnaires were analyzed by geographic categories (small rural/isolated, large rural, and urban). Double selection LASSO with Poisson regression was used to assess the best model when examining the association between health care utilization variables and geographic residence. RESULTS: Among 37,802 participants with RA, urban residents were more likely than small rural residents to use in-person health care by most measures including physician visits and diagnostic tests. Urban residents reported more rheumatologist visits (incidence rate ratio [IRR], 1.22; 95% confidence interval [95% CI], 1.18-1.27) but fewer primary care visits (IRR 0.90; 95% CI 0.85-0.94). Among 8,248 participants with OA, urban residents were also more likely than rural residents to report health care utilization by most measures. CONCLUSION: Individuals residing in urban areas were more likely than those in rural areas to report in-person health care utilization. Specifically, urban residents with RA were more likely to report rheumatologist visits, but less likely to report primary care visits. Less disparity existed in OA health care utilization, although an urban-rural disparity still existed by most measures.

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.

Benefits of Autoantibody Enrichment in Early Rheumatoid Arthritis: Analysis of Efficacy Outcomes in Four Pooled Abatacept Trials.

INTRODUCTION: The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. METHODS: Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration < 1 year, and Disease Activity Score-28 (DAS28) C-reactive protein (CRP) ≥ 3.2 at baseline; non-SPEAR otherwise. Outcomes included: American College of Rheumatology (ACR) 20/50/70 at week 24; mean change from baseline to week 24 for DAS28 (CRP), Simple Disease Activity Index (SDAI), ACR core components; DAS28 (CRP) and SDAI remission. Adjusted regression analyses among abatacept-treated patients compared SPEAR and non-SPEAR patients, and in full trial population estimating how the efficacy of abatacept versus comparators [adalimumab + methotrexate, methotrexate] was modified by SPEAR status. RESULTS: The study included 1400 SPEAR and 673 non-SPEAR patients; most were female (79.35%), white (77.38%), and with a mean age 49.26 (SD 12.86) years old. Around half with non-SPEAR were RF + and three-quarters ACPA +. Stronger improvements from baseline to week 24 were observed in almost all outcomes for abatacept-treated SPEAR versus non-SPEAR patients or versus SPEAR patients treated with comparators. Larger improvements were observed for SPEAR patients among the abatacept-treated population, and more strongly improved efficacy among SPEAR patients for abatacept than comparators. CONCLUSIONS: This analysis, including large patient numbers of early-RA abatacept trials, confirmed beneficial treatment effects of abatacept in patients with SPEAR versus non-SPEAR.

Obesity, Adipokines, and Chronic and Persistent Pain in Rheumatoid Arthritis.

We aimed to determine whether adipokines are associated with pain and polysymptomatic distress in patients with rheumatoid arthritis (RA) over time in a large patient registry. The cohort study was conducted in a subset of Forward; a patient-based multi-disease, multipurpose rheumatic disease registry with patients enrolled from community-based rheumatology practices across the U.S. Adipokines (adiponectin, leptin, and fibroblast growth factor[FGF]-21) were measured on stored serum as part of a multi-analyte panel. Body mass index (BMI), pain, polysymptomatic distress, and other patient-reported outcomes (PROs) were reported on biannual questionnaires. Linear regression was used to evaluate independent associations between BMI, adipokines, and PROs. Cox proportional hazards models evaluated independent associations between adipokines and clinically meaningful changes in pain over time (change in numerical rating>1.1 [range 0-10], sustained over 1 year). Among 645 patients included in these analyses, there were significant differences in RA characteristics, comorbidity, PROs, and adipokines across obesity categories. Of note, severely obese patients were more likely to experience greater pain, polysymptomatic distress, and fatigue. Patients with higher FGF-21 levels had higher pain and polysymptomatic stress at baseline, were more likely to use opioids, and were more likely to have sustained worsening pain over time [HR (per 1 SD) (95% CI): 1.22 (1.02,1.46) P = .03] independent of BMI. Obesity and elevated levels of FGF-21 are associated with pain and polysymptomatic distress in RA. Elevated FGF-21 levels may help identify those at risk of worsening pain trajectories over time, independent of BMI. PERSPECTIVE: This study characterizes the relationship between severe obesity and pain and polysymptomatic distress in patients with rheumatoid arthritis and demonstrates that the adipocytokine fibroblast growth factor-21 is independently associated with pain and predicts a worsening trajectory over time. Further mechanistic studies are needed.

Smoking cessation patterns, usefulness of quitting methods, and tobacco cessation motivators and barriers to quit in patients with rheumatoid arthritis.

OBJECTIVE: Tobacco use is highly discouraged in patients with rheumatoid arthritis (RA) due to related short and long-term health implications. We aimed to evaluate smoking cessation patterns in patients with RA. In addition, we ascertained perceptions on the usefulness of quitting methods, and perceived motivators and barriers to quit. METHODS: We surveyed adults with RA enrolled in the FORWARD Databank who self-identified as former or current tobacco users. RESULTS: Three hundred forty-eight participants completed the survey and responded to the question "do you currently smoke" (former use = 319; current use = 29). Nicotine replacement therapy (NRT) was perceived as extremely/somewhat useful by 31%, followed by individual 27% and group counseling 21%. Experiencing a major health event was the most common motivator to quit. Current users on average smoked 17 cigarettes per day. Six of the 29 current users had used electronic cigarettes in the past 30 days. The most frequent methods used to quit were "cold turkey quitting," NRT, and prescription medicines. Only 8 of the 23 current users had plans to quit or expressed being ready to make changes to quit. Reasons most frequently listed to not quit were using smoking to manage negative emotions, as a pleasurable habit, to manage other addictions, and to provide a sense of control (e.g., to cope with RA). CONCLUSIONS: Current users expressed several negative emotions including coping with the disease and "being a pleasurable habit" when trying to quit. Future cessation programs should address these barriers to support patients with RA. Key Points • First study characterizing the smoking behavior of patients with RA in the USA. Current users were younger, had a shorter disease duration, and worse disease outcomes compared to former smokers. • Former and current users reported similar motivators to quit, with experiencing a major health event being most common. Only about a third of participants who quit or who were still smoking received advice from a health professional. • The most common reasons for not quitting were that smoking help to manage negative emotions and was a pleasurable habit. Future studies should focus on cessation programs that support participants with RA by addressing the unique perceptions about smoking in this population.

Clinical Features Associated With Rate of Fractures in Patients With Systemic Sclerosis: A US Cohort Study.

OBJECTIVE: Systemic sclerosis (SSc) is associated with several specific risk factors for fracture due to the complications of the disease and related medications. The present study was undertaken to examine the relationship between SSc-associated clinical features and fracture rate in a large US cohort. METHODS: Participants with SSc in FORWARD, The National Databank for Rheumatic Diseases, were included (1998-2019). Age- and sex-matched individuals with osteoarthritis (OA) from the same database were included as comparators. The primary end point was self-reported major osteoporotic fracture. Cox proportional hazards models were used to study the associations between risk factors and fractures. RESULTS: The study included 922 individuals (SSc patients, n = 154; OA patients, n = 768). Eighty-seven percent were female, with a mean age of 57.8 years. Fifty-one patients developed at least 1 fracture during a median of 4.2 years (0.5-22.0 years) of follow-up. Patients with SSc had more frequent fractures compared to OA comparators (hazard ratio [HR] 2.38 [95% confidence interval (95% CI) 1.47-3.83]). Among patients with SSc, a higher Rheumatic Disease Comorbidity Index score (HR 1.45 [95% CI 1.20-1.75]) and a higher Health Assessment Questionnaire disability index score (HR 3.83 [95% CI 2.12-6.93]) were associated with more fractures. Diabetes mellitus (HR 5.89 [95% CI 2.51-13.82]) and renal disease (HR 2.43 [95% CI 1.10-5.37]) were independently associated with fracture among SSc patients relative to SSc patients without these comorbidities. CONCLUSION: Our findings highlight factors associated with fracture among patients with SSc. Disability as measured by the HAQ DI is a particularly strong indicator of fracture rate in SSc. Improving SSc patients' functional status, where possible, may lead to better long-term outcomes.

Updating and Validating the Rheumatic Disease Comorbidity Index to Incorporate ICD-10-CM Diagnostic Codes.

OBJECTIVE: To update and validate the Rheumatic Disease Comorbidity Index (RDCI) utilizing International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. METHODS: We defined ICD-9-CM (n = 1,068) and ICD-10-CM (n = 1,425) era cohorts (n = 862 in both) spanning the ICD-9-CM to ICD-10-CM transition in a multicenter, prospective rheumatoid arthritis registry. Information regarding comorbidities was collected from linked administrative data over 2-year assessment periods. An ICD-10-CM code list was generated from crosswalks and clinical expertise. ICD-9- and ICD-10-derived RDCI scores were compared using intraclass correlation coefficients (ICC). The predictive ability of the RDCI for functional status and death during follow-up was assessed using multivariable regression models and goodness-of-fit statistics (Akaike's information criterion [AIC] and quasi information criterion [QIC]) in both cohorts. RESULTS: Mean ± SD RDCI scores were 2.93 ± 1.72 in the ICD-9-CM cohort and 2.92 ± 1.74 in the ICD-10-CM cohort. RDCI scores had substantial agreement in individuals who were in both cohorts (ICC 0.71 [95% confidence interval 0.68-0.74]). Prevalence of comorbidities was similar between cohorts with absolute differences <6%. Higher RDCI scores were associated with a greater risk of death and poorer functional status during follow-up in both cohorts. Similarly, in both cohorts, models including the RDCI score had the lowest QIC (functional status) and AIC (death) values, indicating better model performance. CONCLUSION: The newly proposed ICD-10-CM codes for the RDCI-generated comparable RDCI scores to those derived from ICD-9-CM codes and are highly predictive of functional status and death. The proposed ICD-10-CM codes for the RDCI can be used in rheumatic disease outcomes research spanning the ICD-10-CM era.

Perspectives on Treatment Burden for Methotrexate and Tumor Necrosis Factor Inhibitors Among Patients With Psoriatic Arthritis and Rheumatoid Arthritis: A Qualitative Study.

OBJECTIVE: To describe patients' perspectives on the burden associated with methotrexate (MTX) or tumor necrosis factor inhibitor (TNFi) use in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Between May 2019 and March 2020, patients receiving MTX and/or a TNFi for either PsA or RA were randomly sampled from the FORWARD data bank and were invited to participate in semistructured telephone interviews. Interviews explored patients' perspectives on treatment burden and experiences with MTX and TNFi and were conducted until data saturation was achieved. Interviews were recorded, transcribed, and analyzed using a grounded theory approach and NVivo v12.0 software. RESULTS: Overall, 25 patients with PsA and 24 patients with RA participated in the interviews. Participants were predominantly women (mean age: 67 years). Nine major themes related to treatment burden were explored, including treatment side effects and their management, psychological burden, effect on daily functioning and work participation, challenges with accessing and administering therapies, financial difficulties or economic impact, and family planning or breastfeeding. Patients receiving MTX mostly reported side effects as the major burden, while cost and concerns with accessing and administering medication were major challenges reported by TNFi users. Treatment discontinuation due to lack of effectiveness was high for PsA, while discontinuation due to medication cost was high for RA. CONCLUSION: Patients experience a wide range of burden associated with treatments used for PsA and RA. Health care practitioners should consider these challenges when prescribing therapy and strive toward reducing this burden by understanding patients' concerns and needs and involving them in decision making.

Physical Activity Habits Among Older Adults Living With Rheumatic Disease.

OBJECTIVE: To describe levels of physical activity (PA) in older adults with rheumatic and musculoskeletal diseases (RMDs) and study the association between PA level and patient-reported outcomes. METHODS: Using data from FORWARD, a cross-sectional analysis was performed among adults aged 65 years and older with RMDs to assess the levels of PA. PA was categorized as high (vigorously active for at least 30 minutes, 3 times per week), moderate (moderately active for at least 3 times per week) or low (seldom active). We assessed the self-reported levels of PA among patients with different types of RMDs and assessed the association between levels of PA and PROs, including the 29-item Patient Reported Outcomes Measurement Information System (PROMIS-29) assessment. RESULTS: Among the 3343 eligible participants, rheumatoid arthritis (68%) was the most common RMD. High PA was reported by 457 (13.6%) participants, and 1820 (54.4%) reported moderate activity. Overall, participants reported a median of 7 (IQR 0-15) days of moderate to vigorous level of PA for ≥ 30 min per month. Obese participants were significantly more likely to report low levels of activity (44% of obese compared to 25% of nonobese individuals). Participants with low PA levels had higher (worse) pain scores, higher (worse) Health Assessment Questionnaire-Disability Index scores, higher depression rates, and worse PROMIS-29 scores related to pain, sleep and fatigue. CONCLUSION: Among patients with RMDs, levels of high PA were relatively low among older patients. These observations, though descriptive, support a relationship between physical inactivity and obesity, depression, poor sleep, and fatigue in patients with RMDs.

Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe.

OBJECTIVES: To determine the individual impact of key manifestations of psoriatic arthritis (PsA) on quality of life (QoL), physical function, and work disability. METHODS: Data from the Adelphi 2018 PsA Disease-Specific Programme, a multinational, cross-sectional study of PsA patients, were used. PsA manifestations included peripheral arthritis (number of joints affected), psoriasis (body surface area [BSA]), axial involvement (inflammatory back pain [IBP] and sacroiliitis) enthesitis, and dactylitis. General, and disease-specific QoL, physical function, and work disability were measured with EQ-5D-5L, PsAID-12, HAQ-DI, and WPAI, respectively. Multivariate regression adjusting for potential confounders evaluated the independent effect of PsA manifestations on each outcome. RESULTS: Among the 2222 PsA patients analysed, 77.0% had active psoriasis and 64.4% had peripheral arthritis; 5.9%, 6.8%, 10.2%, and 3.6% had enthesitis, dactylitis, IBP, or sacroiliitis, respectively. Mean EQ VAS scores were significantly poorer in patients with vs. without enthesitis (59.9 vs. 75.6), dactylitis (63.6 vs. 75.4), and with greater peripheral joint involvement (none: 82.5; 1-2 affected joints: 74.1; 3-6 joints: 74.2; >6 joints: 65.0). Significantly worse mean PsAID-12 scores were associated with vs. without enthesitis (4.39 vs. 2.34) or dactylitis (4.30 vs. 2.32), and with greater peripheral joint involvement (none: 1.21; 1-2 joints: 2.36; 3-6 joints: 2.74; >6 joints: 3.92), and BSA (none: 1.49; >3-10%: 2.96; >10%: 3.43). Similar patterns were observed with HAQ-DI and WPAI scores. CONCLUSION: Most PsA manifestations were independently associated with worse general, and PsA-specific QoL, physical function, and work disability, highlighting the need for treatments targeting the full spectrum of PsA symptoms to lower the burden of disease.

A Narrowing Mortality Gap: Temporal Trends of Cause-Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: To examine temporal trends in all-cause and cause-specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA). METHODS: We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non-RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA-related risk of all-cause and cause-specific mortality. RESULTS: Among 29,779 incident RA patients (matched to 245,226 non-RA patients), 9,565 deaths occurred. RA patients were at increased risk of all-cause (adjusted hazard ratio [HRadj ] 1.23 [95% confidence interval (95% CI) 1.20-1.26]), cardiovascular (HRadj 1.19 [95% CI 1.14-1.23]), cancer (HRadj 1.19 [95% CI 1.14-1.24]), respiratory (HRadj 1.46 [95% CI 1.38-1.55]), and infection-related mortality (HRadj 1.59 [95% CI 1.41-1.80]). Interstitial lung disease was the cause of death most strongly associated with RA (HRadj 3.39 [95% CI 2.88-3.99]). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All-cause mortality risk related to RA was lower among those diagnosed during 2012-2017 (HRadj 1.10 [95% CI 1.05-1.15]) compared to 2000-2005 (HRadj 1.31 [95% CI 1.26-1.36]), but still higher than for non-RA controls (P < 0.001). Cause-specific mortality trends were similar. CONCLUSION: Excess RA-related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Although our findings support that RA-related mortality risk is decreasing over time, a mortality gap remains for all-cause and cause-specific mortality in RA.

Looking at fibromyalgia differently - An observational study of the meaning and consequences of fibromyalgia as a dimensional disorder.

OBJECTIVE: Despite data showing that fibromyalgia can be represented as a dimensional disorder, almost all assessments treat fibromyalgia as a dichotomous categorial disorder; and research shows that agreement between community diagnosis of fibromyalgia and fibromyalgia criteria is poor. We investigated the validity of FM as a discrete disorder by exploring the relationships of categorical fibromyalgia, the polysymptomatic distress (PSD) scale, and clinical variables. METHODS: In a databank of 33,972 rheumatic disease patients, we studied the categorical diagnosis of fibromyalgia, the PSD scale separately and divided into severity groups, measures of widespread pain, as well as somatic syndrome questionnaires like the Patient Health Questionnaire-15 (PHQ-15), and clinical pain, global, HAQ disability and quality of life scales (EQ-5D). RESULTS: Clinical and demographic variables became more abnormal with increasing PSD score groups, indicating substantial increase in symptoms and pain. The changes across PSD categories were linear and large. When we compared FM- (PSD 8-11) with FM+ (PSD 12-18) patients we found considerable overlap in scores for pain, HAQ disability, patient global, PHQ-15, psychological status, and other variables. Somatic symptom scores were highly correlated with PSD (r=0.718). There was no evidence of a differential pain effect that was present in FM+ but not FM- subjects. CONCLUSION: Fibromyalgia is more accurately considered a dimensional than a dichotomous disorder. There is vast variability among fibromyalgia positive and negative cases that is governed by the strong and linear relationships between the dimensional PSD scale and clinical variables. The PSD scale provides measurements of the fibromyalgia dimension that support and enlighten categorical fibromyalgia and are an effective tool to measure clinical status and changes. Whatever the mechanism of the pain and symptom increase in fibromyalgia, it appears to operate over the entire fibromyalgia symptom dimension, not just in those with categorical fibromyalgia.