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Objective: To determine whether breast feeding or the use of oral contraceptives (OCs) affects the future risk of rheumatoid arthritis (RA) in a community-based prospective cohort. Methods: A community-based health survey (18 326 women) was linked to regional and national registers, and incident cases of RA were identified. All women with a diagnosis of RA after inclusion in the health survey (n = 136) and four female controls for every case, who were alive and free from RA when the index person was given a diagnosis of RA, were included in a case–control study. Data on lifestyle factors at baseline were derived from a self-administered questionnaire. Potential predictors were examined in logistic regression models. Results: 136 women with incident RA were compared with 544 age-matched controls. A longer history of breast feeding was associated with a reduced risk of RA (OR 0.46 (95% CI 0.24 to 0.91) for women who had breast fed for ⩾13 months and OR 0.74 (95% CI 0.45 to 1.20) for those who had breast fed for 1–12 months, compared with those who had never breast fed). The protective effect of longer breast feeding remained significant after adjustment for smoking and level of education in multivariate models, and point estimates were protective also when the analyses were restricted to parous women. Neither parity nor OC use had any significant effect on the risk of RA. Conclusion: In this study, long-term breast feeding, but not OC use, was associated with a significant reduction in the risk of RA. [ABSTRACT FROM PUBLISHER]

Background: Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity.Objective: To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis.Methods: Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up.Results: ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64).Conclusion: Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence.Methods: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews.Results: ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity.Conclusion: There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA)., Methods: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population., Results: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6)., Conclusions: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking., Methods: Through Swedish registers, we identified 13 493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age., Results: Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%)., Conclusions: As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered., Competing Interests: Competing interests: Karolinska Institutet, with JA as principal investigator, has or has had research agreements with AbbVie, Astra-Zeneca, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, mainly in the context of safety monitoring of biologics via ARTIS/Swedish Biologics Register. CT has received speaker fees from AbbVie, BMS, Nordic Drugs, Pfizer and Roche., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision., Methods: Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities., Results: Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends., Conclusions: Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed., Competing Interests: Competing interests: JA: principal investigator for agreements between Karolinska Institutet and Abbvie, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis and Sanofi for safety monitoring of antirheumatic therapies (ARTIS). KC: consultancy fees and speaker’s honoraria from Eli Lilly, Abbvie and Pfizer. NF is employed by the Medical Products Agency (MPA), which is a governmental body. The views in this article may not represent the views of the MPA. AK: former employee of Sanofi. CT: Research grant from Bristol Myers Squibb, consultancy fees and speaker’s honorarium from Roche, and speaker’s honoraria from Abbvie and Pfizer., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period., Methods: Consecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests., Results: At inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was -0.33 (95 % CI -0.57 to -0.08) in men and -0.07 (-0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value -0.35; 95 % CI -0.61 to -0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was -0.05 (-0.29 to 0.19) and for women 0.06 (-0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen., Conclusions: In this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5 years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare several methods of missing data imputation for function (Health Assessment Questionnaire) and for disease activity (Disease Activity Score-28 and Clinical Disease Activity Index) in rheumatoid arthritis (RA) patients., Methods: One thousand RA patients from observational cohort studies with complete data for function and disease activity at baseline, 6, 12 and 24 months were selected to conduct a simulation study. Values were deleted at random or following a predicted attrition bias. Three types of imputation were performed: (1) methods imputing forward in time (last observation carried forward; linear forward extrapolation); (2) methods considering data both forward and backward in time (nearest available observation-NAO; linear extrapolation; polynomial extrapolation); and (3) methods using multi-individual models (linear mixed effects cubic regression-LME3; multiple imputation by chained equation-MICE). The performance of each estimation method was assessed using the difference between the mean outcome value, the remission and low disease activity rates after imputation of the missing values and the true value., Results: When imputing missing baseline values, all methods underestimated equally the true value, but LME3 and MICE correctly estimated remission and low disease activity rates. When imputing missing follow-up values at 6, 12, or 24 months, NAO provided the least biassed estimate of the mean disease activity and corresponding remission rate. These results were not affected by the presence of attrition bias., Conclusion: When imputing function and disease activity in large registers of active RA patients, researchers can consider the use of a simple method such as NAO for missing follow-up data, and the use of mixed-effects regression or multiple imputation for baseline data., Competing Interests: Competing interests: DM: none declared for this work. KL: none declared for this work. KP: received honoraria for lectures: AbbVie, Roche, MSD, UCB, Pfizer, Amgen, Egis, BMS. CT: none declared for this work. MJS: none declared for this work. EKK: none declared for this work. AF: none declared for this work. DC: none declared for this work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX)., Methods: In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) ≥2.6 or a change in DAS28 (ΔDAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28., Results: 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with ≥1 ΔDAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005)., Conclusions: In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission., Trial Registration Number: NCT00808509.