Lars Erik Kristensen

The effect of circumstances and exposures early in life on the risk of developing ankylosing spondylitis (AS) is largely unknown. The purpose of this study was to determine whether perinatal characteristics predict development of AS. AS cases (n = 1960; 59 % men) were defined as listed with a diagnosis of AS at least once in the Swedish National Patient Register and registered in the Swedish Medical Birth Register (born ≥1973). Population controls were retrieved from the Swedish Population Register (n = 8378; mean 4.3 controls/case), matched on birth year, sex and county. Odds ratios (OR) for developing AS were determined through conditional logistic regression, with regard to: birth weight, birth order, season of birth, maternal age, gestational length, size for gestational age, type of birth, mode of delivery, congenital malformations, mothers’ country of birth, mothers’ civil status and size of delivery unit. In the univariate analyses statistically significant increases in risk for developing AS were observed for having older siblings (OR 1.18; 95 % Cl 1.06–1.30). No association was observed for the remainder of analysed exposures, although there was a weak association with birth weight below 3000 g (OR 1.19; 95 % CI 1.04–1.37), though not for “low birth weight” <2500 g (OR 0.90; 95 % CI 0.70–1.16). The increase in risk associated with having older siblings was consistent in a multivariate analysis adjusting for possible confounders (OR 1.23; 95 % Cl 1.09–1.39). The direction and magnitude of the point estimates were also consistent in several sensitivity analyses and when stratifying by sex. Having older siblings was associated with an increased risk for developing AS. These results need to be repeated and confirmed in other cohorts.

The relationship between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) is currently debated. Using observational data from the South Swedish Arthritis Treatment Group register, we thus aimed to compare clinical development and treatment adherence between nr-axSpA and AS patients during three years of anti-TNF (tumor necrosis factor) therapy in clinical practice, and to explore the impact of inflammatory activity measured by CRP (C-reactive protein) at treatment initiation. Nr-axSpA and AS patients (n = 86/238) in southern Sweden, commencing anti-TNF therapy 1999-2011, were followed during three years. Anti-TNF cessation was defined as stopping therapy, without restarting another anti-TNF agent within three months. Differences in the three year developments of patient’s visual analogue scale (VAS) scores for global health and pain, EuroQol 5-Dimensions utility, evaluator’s global disease activity assessment, CRP, and ESR (erythrocyte sedimentation rate) were assessed by repeated ANOVA. Anti-TNF adherence was compared by Log rank test and Cox regression. In a subanalysis, the same outcomes were studied after splitting both groups into patients with/without baseline CRP elevation. Nr-axSpA patients were more often female and had lower acute phase reactants at baseline. Apart from CRP, which remained lower in the nr-axSpA group throughout follow-up (p = 0.004), no between-group differences were detected regarding clinical developments (p >0.1 for all comparisons) or anti-TNF adherence (hazard ratio: 1.1 (95 % CI 0.7 to 1.8) for the nr-axSpA vs. AS group) during three years. Elevated baseline CRP was similarly associated with superior clinical outcomes and treatment adherence in both groups. With the exception of constantly lower CRP levels in the nr-axSpA group, three years anti-TNF therapy resulted in similar clinical outcomes and treatment adherence in nr-axSpA and AS patients, thus strengthening the hypothesis that these diagnoses represent different aspects/phases of the same disease.

Objective.: Because new modes of action for the treatment of psoriatic arthritis (PsA) are emerging, it is important to understand the use of switching to a second or third antitumor necrosis factor (anti-TNF) agent. This study investigated drug survival and treatment response rates of patients with PsA undergoing second- and third-line anti-TNF therapy.Methods.: Patients with PsA were monitored in a prospective, observational study. Patients who switched anti-TNF therapy once (first-time switchers, n = 217) or twice (second-time switchers, n = 57) between January 2003 and March 2012 were studied. American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) good response at 3 and 6 months, as well as drug survival, were reported and further analyzed using the Cox and logistic regression models.Results.: Median age for first-time switchers was 47 years and 42% were men. The corresponding values for second-time switchers were 48 years and 40% men. Three-month ACR20 Lund Efficacy Index (LUNDEX) response was achieved by 47% of first-time and 22% of second-time switchers; ACR50 LUNDEX rates were 21% and 14%, ACR70 LUNDEX rates were 12% and 2%, and EULAR good LUNDEX rates were 26% and 10%, respectively. Median drug survival time for patients switching anti-TNF for the first time was 64 months (95% CI 31–97) compared with 14 months (95% CI 5–23) for second-time switchers. Identified baseline predictor of ACR20 response to second-line treatment was the 28-joint Disease Activity Score values at baseline (OR 1.45, 95% CI 1.01–2.10), while higher Health Assessment Questionnaire scores predicted premature drug withdrawal (HR 1.60, 95% CI 1.03–2.48).Conclusion.: Response rates of first-time anti-TNF switchers are moderate, while the inferior response rates of second-time switchers suggest other therapeutic options should be considered in this situation.

Introduction: Prevalence estimates of ankylosing spondylitis vary considerably, and there are few nationwide estimates. The present study aimed to describe the national prevalence of clinically diagnosed ankylosing spondylitis in Sweden, stratified according to age, sex, geographical, and socio-economic factors, and according to subgroups with ankylosing spondylitis-related clinical manifestations and pharmacological treatment. Methods: All individuals diagnosed with ankylosing spondylitis according to the World Health Organization International Classification of Disease codes, between 1967 and 2009, were identified from the National Patient Register. Data regarding disease manifestations, patient demographics, level of education, pharmacological treatment, and geographical region were retrieved from the National Patient Register and other national registers. Results: A total of 11,030 cases with an ankylosing spondylitis diagnosis (alive, living in Sweden, and 16 to 64 years old in December 2009) were identified in the National Patient Register, giving a point prevalence of 0.18% in 2009. The prevalence was higher in northern Sweden, and lower in those with a higher level of education. Men had a higher prevalence of ankylosing spondylitis (0.23% versus 0.14%, P < 0.001), a higher frequency of anterior uveitis (25.5% versus 20.0%, P < 0.001) and were more likely to receive tumor necrosis factor inhibitors than women (15.6% versus 11.8% in 2009, P < 0.001). Women were more likely than men to have peripheral arthritis (21.7% versus 15.3%, P < 0.001), psoriasis (8.0% versus 6.9%, P = 0.03), and treatment with oral corticosteroids (14.0% versus 10.4% in 2009, P < 0.001). Conclusion: This nationwide, register-based study demonstrated a prevalence of clinically diagnosed ankylosing spondylitis of 0.18%. It revealed phenotypical and treatment differences between the sexes, as well as geographical and socio-economic differences in disease prevalence.

Objective: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs.Methods: We performed a national register‐based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987–2009. Treatment exposure was assessed time dependently based on the prescription drug register from 2006–2009, adjusting for sociodemographics and comorbidities derived from national population‐based registers.Results: Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal, or renal adverse events were seen among the 3 exposure groups. Patients unexposed to NSAIDs had more baseline comorbidities and an increased relative risk for congestive heart failure events during the study period (2.0, 95% confidence interval [95% CI] 1.3–3.2). The relative risk for atherosclerotic events was nonsignificant when compared to the nonselective NSAID group (1.0, 95% CI 0.7–1.5), while the relative risk for gastrointestinal events was lower for unexposed patients (0.5, 95% CI 0.4–0.7).Conclusion: Overall, serious adverse events related to nonselective NSAIDs, etoricoxib, and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerably more baseline comorbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAIDs in clinical practice.

Ankylosing spondylitis (AS) is associated with several extra-articular manifestations. Nephrolithiasis (NL) has not been recognized as one of those, however, several factors known to increase the risk of NL are at play in AS patients. The objective was to estimate rates and predictors of NL in Swedish patients with AS compared to the general population. We performed a prospective population-based nationwide cohort study based on linkage of data from Swedish registries. 8,572 AS patients were followed for 49,258 person-years (py) and 39,639 matched general population comparators were followed for 223,985 py. Patients were followed prospectively together with comparator subjects from January 2001 through December 2009. The first occurrence of NL during follow-up was the primary outcome. Hazard Ratios (HR) were used to compare these rates adjusting for comorbidities and treatment, and to assess predictors for NL. Mean age at study entry was 46 years (inter quartile range 36–56 years), 65% were males. Based on 250 vs. 466 NL events, the adjusted HR of NL in AS patients was 2.1 (95%CI 1.8 to 2.4). Predictors of NL within the AS group included prior diagnosis of inflammatory bowel disease (IBD) (HR 2.3; 95%CI 1.7 to 3.3), prior diagnosis of NL (HR 16.4; 95%CI 11.5 to 23.4), and patients receiving anti-TNF treatment (HR 1.6; 95%CI 1.2 to 2.1). Male sex was a risk factor for NL both in AS patients and in the general population. The risk for residual confounding and inability to study the chemical nature of NL were considered the main limitations of the study. Patients with AS are at increased risk of NL, which may be considered a novel extra-articular manifestation. Previous history of NL, IBD, AS disease severity and male sex were identified as predictors of NL in AS.

Ankylosing Spondylitis (AS) is a chronic inflammatory disease with onset in young adults, but little is known about the prevalence in older age groups. Furthermore, there is very limited information of health status of elderly patients with AS. Our objective was to estimate the prevalence of moderate to severe radiographic sacroiliitis in elderly men and its impact on health.

Objective To study long-term work disability before and after tumour necrosis factor (TNF)-antagonist therapy in patients with psoriatic arthritis (PsA). Methods Using the population-based South Swedish Arthritis Treatment Group Register, we identified 191 patients with PsA (median age 43 years, range 18–58 years, 54% men), who between January 2003 and December 2007 started treatment with adalimumab, etanercept or infliximab. We linked data to the Swedish Social Insurance Agency and calculated the proportion of work disability in 30-day intervals from 12 months before the start of treatment until 3 years after. For each patient with PsA we randomly selected four matched reference subjects from the general population. Results At treatment initiation 67% of the patients with PsA were work disabled—that is, either on sick leave (41.5%) or receiving a disability pension (25.3%). Patients sustaining treatment were, on average, work disabled 12.5 days a month at treatment initiation declining to 10.6 days a month after 3 years of treatment. Patients for whom the first treatment course failed were work disabled 16.5 days at treatment start decreasing to 15.6 days after 3 years. The background population were 2.5 days and 3.0 days off work each month, respectively. Regression modelling identified prior work disability status, anti-TNF treatment failure, higher age, female gender and longer disease duration as significant predictors of working disability. Conclusions There was a decline in net work disability after initiation of anti-TNF treatment in patients with PsA. Patients withdrawing from treatment had a 50% increased risk of being work disabled. Prior work disability, higher age, female gender and longer disease duration were also associated with long-term work disability.

Objective: To study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti–tumor necrosis factor (anti‐TNF) therapy in rheumatoid arthritis (RA) patients.Methods: Patients with RA initiating their first course of anti‐TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR 1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010.Results: A total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18–29%) with low, 39% (95% CI 35–43%) with moderate, and 40% (95% CI 36–44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively.Conclusion: STR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2‐ to 3‐fold increased likelihood of responding according to ACR50 criteria.