Incident Rheumatoid Arthritis Cohort Research Articles

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

ObjectivesTo compare the onset and trajectory of multimorbidity between individuals with and without rheumatoid arthritis (RA).MethodsA matched, retrospective cohort study was completed in a large, US commercial insurance database (MarketScan)...

Treatment Strategies in Early Rheumatoid Arthritis Methotrexate Management: Results From a Prospective Cohort.

To assess real-world practice patterns surrounding treatment initiation and adjustments over time for methotrexate (MTX) and non-MTX-based treatment strategies in early rheumatoid arthritis (RA). We studied a multicenter, incident early RA cohort (enrolled 2007-2017 within 1 year of symptoms) who fulfilled American College of Rheumatology/European League Against Rheumatism criteria. Adult patients with RA were eligible if treatment with MTX (± other disease-modifying antirheumatic drugs [DMARDs]) was initiated within 90 days of cohort entry. We compared time until treatment change for 4 initial MTX-based therapies and time to second treatment change after the first change. The definition of treatment change included changing of route for MTX monotherapy, adding or stopping a DMARD or biologic, and changing dose/frequency of a DMARD or biologic. There was great variability of treatment at initiation and during therapy adjustment. In 1,484 patients with early RA, the majority initiated MTX monotherapy (oral or subcutaneous [SC]). Patients receiving SC MTX monotherapy changed treatment less (45% versus 79%) and remained on treatment longer (hazard ratio [HR] 0.52 [95% confidence interval (95% CI) 0.4-0.67]) than those receiving oral MTX monotherapy. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those adults taking biologics and who were receiving triple therapy had a longer time without treatment change (HR 0.26 [95% CI 0.16-0.42] and HR 0.57 [95% CI 0.38-0.85], respectively). We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support the use of SC MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those patients initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy.

Joint Estimation of Remission and Response for Methotrexate-Based DMARD Options in Rheumatoid Arthritis: A Bivariate Network Meta-Analysis.

ObjectiveTo jointly estimate American College of Rheumatology (ACR50) response (a more commonly reported outcome) and remission (a more clinically relevant outcome) for methotrexate (MTX)‐based treatment options in rheumatoid arthritis (RA).MethodsWe conducted a bivariate network meta‐analysis (NMA) to compare MTX monotherapy and MTX‐based conventional and biologic disease‐modifying antirheumatic drug (DMARD) combinations for RA. The correlation between the outcomes was derived from an incident RA cohort study, whereas the treatment effects were derived from randomized trials in the network of evidence. The analyses were conducted separately for MTX‐naïve and MTX–inadequate response (IR) populations in a Bayesian framework with uninformative priors.ResultsFrom the cohort study, the correlation between ACR50 response and Disease Activity Score 28 remission at 6 months was moderate (Pearson correlation coefficient = 0.58). In the bivariate NMA for MTX‐naïve populations, most combinations of MTX with either biologic or tofacitinib were statistically superior to MTX alone for both ACR50 response and remission. Triple therapy (MTX + sulfasalazine + hydroxychloroquine) was the only nonbiologic DMARD statistically superior to MTX for either ACR50 response (odds ratio [OR] 95% credible interval: 2.1 [1.0, 4.3]) or remission (OR: 2.5 [1.0, 5.8]). In the MTX‐IR analysis, all treatments except MTX + sulfasalazine were statistically superior to MTX alone. Compared to analyzing the outcomes separately, the bivariate model often resulted in more precise estimates and allowed remission to be estimated for all treatments.ConclusionBorrowing the strength of correlation between outcomes allowed us to demonstrate a statistically significant benefit for remission across most MTX‐based DMARD combinations, including triple therapy.

Investigating Asthma, Allergic Disease, Passive Smoke Exposure, and Risk of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and asthma, passive smoke exposure, and age at start of smoking. For this case-control study, we identified 1,023 cases of RA (175 incident) within a single-center biobank population, using a rules-based algorithm that combined self-report with 2 diagnostic codes. Exposures were self-reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. After adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 [95% CI 1.04-1.58; P = 0.02]) but not the incident RA cohort (OR 1.17 [95% CI 0.66-2.06; P = 0.60]). History of allergic disease was associated with RA in both the full cohort (OR 1.30 [95% CI 1.12-1.51; P < 0.001]) and the incident RA cohort (OR 1.61 [95% CI 1.11-2.33; P = 0.01]), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 [95% CI 1.08-1.75; P = 0.01]) and showed a trend toward significance in the incident RA cohort (OR 1.83 [95% CI 0.97-3.45; P = 0.06]). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 [95% CI 1.00-1.06; P = 0.03]) or the incident RA cohort (OR 1.00 [95% CI 0.92-1.08; P = 0.98]). Asthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA.

Risk of Incident Chronic Obstructive Pulmonary Disease in Rheumatoid Arthritis: A Population-Based Cohort Study.

Studies have demonstrated a link between chronic obstructive pulmonary disease (COPD) and inflammation, raising the question whether chronic inflammatory conditions, such as rheumatoid arthritis (RA), predispose to COPD. Our objective was to evaluate the risk of incident COPD hospitalization in RA compared to the general population. We studied a population-based incident RA cohort with matched general population controls, using administrative health data. All incident RA cases in British Columbia who first met RA definition between January 1996 and December 2006 were selected using previously published criteria. General population controls were randomly selected, matched 1:1 to RA cases on birth year, sex, and index year. COPD outcome was defined as hospitalization with a primary COPD code. Incidence rates, 95% confidence intervals (95% CIs), and incidence rate ratios (IRRs) were calculated for RA and controls. Multivariable Cox proportional hazards models estimated the risk of COPD in RA compared to the general population after adjusting for potential confounders. Sensitivity analyses were performed to test the robustness of the results to the possible confounding effect of smoking, unavailable in administrative data, and to COPD outcome definitions. The cohorts included 24,625 RA individuals and 25,396 controls. The incidence of COPD hospitalization was greater in RA than controls (IRR 1.58, 95% CI 1.34-1.87). After adjusting for potential confounders, RA cases had a 47% greater risk of COPD hospitalization than controls. The increased risk remained significant after modeling for smoking and with varying COPD definitions. In our population-based cohort, individuals with RA had a 47% greater risk of COPD hospitalization compared to the general population.

Smoking Behavior Changes in the Early Rheumatoid Arthritis Period and Risk of Mortality During Thirty-Six Years of Prospective Followup.

To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality. We identified an incident RA cohort in the Nurses' Health Study (NHS; 1976-2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within 4 years of the RA/index date. We used Cox regression to obtain hazard ratios (HRs) for mortality, comparing sustained smoking cessation to continued smoking. Among 121,700 women in the NHS, we identified 938 with incident RA matched to 8,951 non-RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period, compared to 36.1% of comparators (odds ratio for sustained cessation 1.18 [95% confidence interval (95% CI) 0.88, 1.58]). There were 313 deaths (33.4%) in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58 [95% CI 0.33, 1.01]) and comparison (HR 0.47 [95% CI 0.39, 0.58]) cohorts. Women with RA had higher mortality for >5 post-RA pack-years (HR 3.67 [95% CI 2.80, 4.81]) than comparators with >5 post-index pack-years (HR 1.88 [95% CI 1.62, 2.17]; P < 0.001 for interaction; reference: ever-smoker non-RA women with 0 post-index pack-years). Sustained smoking cessation within 4 years of RA diagnosis reduced mortality risk, with a similar effect observed among non-RA comparators. Smoking >5 pack-years after RA diagnosis significantly increased mortality beyond the risk of non-RA comparators.

Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population—closing the mortality gap

ObjectiveExcess mortality in rheumatoid arthritis (RA) is expected to have improved over time, due to improved treatment. Our objective was to evaluate secular 5-year mortality trends in RA relative to...

Risk of Developing Rheumatoid Arthritis in Adults with Asthma: A Population-Based Case-Control Study

Mary C. Rolfes, Youn Ho Shin, MD, Chung I. Wi, MD, Cynthia S. Crowson, MS, Richard S. Pendegraft, Euijung Ryu, PhD, Young J. Juhn, MD, MPH; Mayo Medical School, Rochester, MN, Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea, South Korea, Mayo Clinic, Rochester, MN, Dept of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN. RATIONALE: The relationship between asthma and the risk of systemic inflammatory disease such as rheumatoid arthritis (RA) is poorly understood. We determined whether asthma status is associated with the risk of incident RA among adults. METHODS: We conducted a retrospective population-based case-control study, which enrolled a population-based incident RA cohort (2004-2007) and their 1:1 birth yearand gender-matched controls residing in Olmsted County, MN. We performed comprehensive medical record reviews to ascertain asthma status of cases and controls using predetermined criteria for asthma. The frequency of a history of asthma prior to index date was compared between cases and their matched controls. Data were fit to logistic regression models to calculate odds ratios and the corresponding 95% confidence interval (CI). RESULTS: We enrolled 136 RA cases and 134 controls in the study, of whom 84 (31.1%) were male and 256 (94.8%) were Caucasians. The median ages at the index date were 52.4 years for the RA cases and 53.0 years for controls. Of the 136 RA cases, 38 (28%) had a history of asthma, whereas 21 of 134 controls (16%) had a history of asthma (adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.18-3.97, p50.013) after adjusting for age and sex. The similar trends were observed when a physician diagnosis of asthma was used for ascertaining asthma status (aOR, 2.39; 95% CI, 1.27-4.50, p50.007). CONCLUSIONS: Patients with asthma as a T-helper 2 condition had a significantly higher risk of RA as a T-helper 1 proinflammatory condition than healthy individuals.

Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients.

BackgroundCardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA.Methods and ResultsA retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time‐varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD‐related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12–0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13–0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively.ConclusionIn this hypothesis‐generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high‐risk patients.

FRI0410 Rheumatoid arthritis (RA) care: Geographic disparities and impact of primary care physicians on access to rheumatologists

BackgroundEarlier population-based assessments have demonstrated that many Canadians are not provided optimal RA therapy.1 This is especially true for seniors with RA. Little is known about potential barriers that limit...

Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid arthritis

ObjectiveIn contrast with the wealth of data on ischaemic heart disease in rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite the high clinical and aetiological relevance, there...

Increased Incidence and Impact of Upper and Lower Gastrointestinal Events in Patients with Rheumatoid Arthritis in Olmsted County, Minnesota: A Longitudinal Population-based Study

To assess the incidence and mortality impact of upper and lower gastrointestinal (GI) events in rheumatoid arthritis (RA) compared to non-RA subjects. We identified incident upper and lower GI events and estimated their incidence rates using person-year methods in a population-based incident RA cohort of residents of Olmsted County, Minnesota, USA (1987 American College of Rheumatology criteria first fulfilled between January 1, 1980, and January 1, 2008) and non-RA subjects from the same population. The study included 813 patients with RA and 813 non-RA subjects (mean followup 10.3 and 10.8 yrs, respectively); 68% women; mean age 55.9 yrs in both cohorts. The rate of upper GI events/100 person-years was 2.9 in RA versus 1.7 in the non-RA cohort (rate ratio 1.7, 95% CI 1.4, 2.2); for lower GI events, the rates were 2.1 in RA versus 1.4 in the non-RA cohort (rate ratio 1.5, 95% CI 1.1, 1.9). The incidence of upper GI bleed, perforation, ulcer, obstruction, and any upper GI event in RA declined over calendar time; the incidence of lower GI events remained unchanged. Exposure to glucocorticoids, prior upper GI disease, abdominal surgery, and smoking were associated with lower GI events in RA. Both upper and lower GI events were associated with increased mortality risk in RA. There is increased risk of serious upper and lower GI events in RA compared to non-RA subjects, and increased GI-related mortality in RA. Prominent declines in incidence of upper, but not lower GI events in RA highlight the need for studies investigating lower GI disease in patients with RA.

Quality care in seniors with new‐onset rheumatoid arthritis: A Canadian perspective

To estimate the percentage of seniors with rheumatoid arthritis (RA) receiving disease-modifying antirheumatic drugs (DMARDs) within the first year of diagnosis. We assembled an incident RA cohort from Ontario physician billing data for 1997-2006. We used a standard algorithm to identify 24,942 seniors with RA based on ≥ 2 billing codes ≥ 60 days apart but within 5 years. Drug exposures were obtained from pharmacy claims data. We followed subjects for 1 year, assessing if they had been exposed (defined as ≥ 1 prescription) to 1 or more DMARDs within the first year of RA diagnosis. We assessed secular trends and differences for subjects who had received rheumatology care (defined as ≥ 1 rheumatology encounter) versus those who had not. In total, only 39% of the 24,942 seniors with new-onset RA identified over 1997-2006 were exposed to DMARD therapy within 1 year of diagnosis. This increased from 30% in 1997 to 53% in 2006. Patients whose care involved a rheumatologist were more likely to be exposed to DMARDs than those who had no rheumatology care. In 2006, 67% of subjects receiving rheumatology care were exposed to DMARDs versus 21% of those with no rheumatology care. Improvements in RA care have occurred, but more efforts are needed. Subjects receiving rheumatology care are much more likely to receive DMARDs as compared to those with no rheumatology care. This emphasizes the key role of rheumatologists.