Sick leave and disability pension following delivery in women with systemic lupus erythematosus.

OBJECTIVE: To investigate sickness benefits following delivery in mothers with systemic lupus erythematosus (SLE) and mothers without SLE. METHOD: SLE and non-SLE mothers, matched by age and month of delivery, with a singleton liveborn (2004-2008), were identified from the Swedish Lupus Linkage cohort. Work loss (sum of sick leave and disability pension) was studied from 1 year prenatally to 3 years postpartum. Adjusted logistic regression models of covariates associated with > 30 days of work loss in the first and second years postpartum were estimated in SLE mothers. RESULTS: Among 130 SLE mothers and 440 non-SLE mothers, SLE mothers were more likely to have work loss from the prenatal year (42% vs 16%) to 3 years postpartum (49% vs 15%). In SLE mothers, work loss was on average 61 ± 112 days (mean ± sd) in the prenatal year and 38 ± 83 days in the first year postpartum, which increased to 71 ± 114 days in the third year postpartum. Having > 30 days of sick leave in the year of delivery [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.5-12.9] and ≤ 12 years of education (OR 2.6, 95% CI 1.1-6.0) were associated with work loss in the first year postpartum. No covariates were associated with work loss in the second year postpartum. CONCLUSION: SLE mothers more often had work loss in the prenatal year to 3 years postpartum compared to non-SLE mothers. Lower education and sick leave in the year of delivery were associated with a higher odds of work loss in the first year postpartum in SLE.

Infections increase the risk of developing Sjögren's syndrome.

OBJECTIVE: Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS). METHODS: Patients with pSS in Sweden (n = 945) and matched controls from the general population (n = 9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0 years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption. RESULTS: A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6-2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody-positive pSS (OR 2.7, 95% CI 2.0-3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8-4.7) and without autoantibodies (OR 2.1, 95% CI 1.1-3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody-positive pSS (OR 3.2, 95% CI 1.8-5.5 and OR 2.7, 95% CI 1.7-4.2). Furthermore, a dose-response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS. CONCLUSIONS: Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody-positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.

Endometriosis and systemic lupus erythematosus: a population-based case-control study.

OBJECTIVE: To investigate the association between endometriosis and systemic lupus erythematosus (SLE) in prospectively collected population-based data. METHODS: We conducted a case-control study using Swedish registers, identifying female SLE cases from the National Patient Register and female controls sampled from the general population matched on birth year, sex and county during 1964-2011. We identified endometriosis diagnoses from the National Patient Register using ICD codes. We estimated odds ratios and 95% confidence intervals using conditional logistic regression models. RESULTS: We identified 2834 cases of SLE and 14,164 controls. Seventy-eight cases were diagnosed with endometriosis prior to their SLE diagnosis and 288 controls were diagnosed prior to the index date. We observed a significant association between endometriosis and subsequent SLE with an odds ratio of 1.39 (95% confidence interval = 1.09-1.78). The association was similar when requiring a laparoscopy/laparotomy within six months of the endometriosis diagnosis (odds ratio = 1.33; 95% confidence interval = 0.84-2.12) while the association was stronger when restricted to endometriosis diagnosed at the same time as hysterectomy (odds ratio = 2.26; 95% confidence interval = 1.47-3.64). CONCLUSIONS: Our findings suggest an association between endometriosis and SLE. Future prospective studies with extended follow-up will be necessary to clarify whether this association is influenced by the timing and severity of endometriosis diagnosis.

Perinatal risk factors for future SLE: a population-based nested case-control study.

OBJECTIVE: To investigate the association between perinatal characteristics and the offspring's risk of lupus using population-based registers in Sweden. METHODS: We conducted a nested case-control study, identifying systemic lupus erythematosus (SLE) cases from the National Patient Register and controls sampled from the general population matched on birth year, sex, and residential county. We obtained data on the mother's health and age during pregnancy and characteristics of labor and delivery from the Medical Birth Register (births from 1973 through 2008) for cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models overall and separately for males and females. RESULTS: We identified 774 cases and 3337 controls. Age at which SLE was first observed ranged from 0 to 36 years old. High birth weight was not a risk factor for SLE and did not differ by sex. Males had a 2.4-fold increased odds of SLE if born preterm (<37 weeks; OR = 2.41; 95% CI 1.09, 5.36). Birth order was significantly associated with SLE, particularly among females (first born vs. not OR = 0.77, 95% CI 0.64, 0.94; continuous birth order OR = 1.12. 95% CI 1.02, 1.24). CONCLUSION: Being born first was associated with reduced odds of SLE and the odds of SLE increased by 12% for every additional birth. Preterm birth was associated with increased odds in males only. Unlike previous work, high birth weight was not a risk factor for SLE.

Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab.

OBJECTIVE: To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy). RESULTS: During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001). CONCLUSIONS: Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.

The Swedish Rheumatology Quality Register: optimisation of rheumatic disease assessments using register-enriched data.

New therapeutic options are constantly emerging for the treatment of rheumatic diseases. To evaluate the safety and efficacy of newly introduced anti-rheumatic treatment alternatives, registers are an important source of information. The Swedish Rheumatology Quality Register (SRQ) collects clinical data on patients with rheumatoid arthritis, as well as other rheumatic diseases, and may be enriched with data on comorbid conditions, prescription drug dispensings, and mortality from national data sources in Sweden. In this setting, many different outcomes can be investigated over a long period of time in a diverse population of patients recruited in daily clinical practice.

Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission.

OBJECTIVE: The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. METHODS: A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52-56 weeks of follow-up. RESULTS: Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001). CONCLUSIONS: The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.