Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.

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.

Healthcare professionals' perceptions of working on lifestyle management for patients with early rheumatoid arthritis - a qualitative study.

AIM: To explore HPs' perceptions of working on lifestyle management for patients with early rheumatoid arthritis (RA). METHODS: In this qualitative study, individual interviews were conducted with 20 HPs. Qualitative content analysis was used, and three categories and six subcategories were identified. RESULTS: HPs' perceptions of working on lifestyle management for patients with early RA revealed a need for commitment from different levels. This included commitment from healthcare managers and organizations prioritizing work on lifestyle management and providing competence development for HPs. Commitment within the team regarding coordination of interdisciplinary teamwork and development of a structured lifestyle management approach, and commitment to involving patients in lifestyle management, by facilitating patient engagement and a person-centred approach. CONCLUSIONS: HPs' perceptions of working on lifestyle management for patients with early RA revealed that commitment from healthcare managers, organizations, and the interdisciplinary team was essential to facilitate collaboration, patient involvement, and a person-centred approach.

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme.

OBJECTIVE: Longitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). METHODS: Nationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. RESULTS: There were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. CONCLUSION: Data from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks.

Elevated fecal levels of the inflammatory biomarker calprotectin in early systemic sclerosis.

Knowledge on gastrointestinal manifestations in early systemic sclerosis (SSc) is limited. We have investigated gastrointestinal inflammation in SSc at the time of diagnosis using the inflammatory biomarker Fecal calprotectin (F-cal). Consecutive patients with suspected SSc were characterized in relation to the 2013 classification criteria for SSc and classified as SSc or SSc-like disease. F-cal levels were measured with a polyclonal ELISA (Calpro A/S, Lysaker, Norway) and levels above 50 µg/g were considered elevated. F-cal levels were compared to those of control subjects without rheumatic disease. Of 137 patients with suspected SSc, 92 were classified as SSc and 45 as SSc-like disease. Median (interquartile range) disease duration among the SSc participants was 2.5 (1.2, 4.6) years. A substantial proportion of participants classified as SSc (35/92, 38%) and SSc-like disease (14/45, 31%) exhibited elevated F-cal compared to the control group (3/41, 7.3%; p < 0.001 and p = 0.007, respectively). Elevated F-cal was associated with proton pump inhibitor usage (OR 7.14; 95% CI 2.56-29.93; p < 0.001). We conclude that elevated F-cal is present in a subgroup of patients with SSc at the time of diagnosis, suggesting that that GI inflammation may be present in this patient group early in the disease course. F-cal did not exhibit potential to differentiate SSc from SSc-like disease.

How good is the agreement between clinical diagnoses and classification criteria fulfilment in axial spondyloarthritis? Results from the SPARTAKUS cohort.

OBJECTIVES: To study the agreement between clinical axial spondyloarthritis (axSpA) diagnoses and fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) axSpA and modified New York (mNY) classification criteria, and to compare disease/health status between axSpA subtypes. METHOD: Patients with prevalent, clinical axSpA attending a rheumatology clinic were enrolled in a cross-sectional study. Assessments included physical evaluation, laboratory testing, questionnaires, and appropriate imaging, allowing classification. Standard axSpA outcome measures were compared between patients fulfilling mNY/radiographic versus non-radiographic axSpA (r-axSpA/nr-axSpA) criteria. RESULTS: Of 239 consecutively included patients, 141 fulfilled ASAS r-axSpA and/or mNY criteria, while 57 fulfilled nr-axSpA criteria. The agreement between r-axSpA and mNY criteria fulfilment was 94%. The positive predictive value (PPV) of a clinical ankylosing spondylitis (AS) diagnosis for mNY criteria fulfilment was 71%; the PPV of an undifferentiated axSpA (u-axSpA) diagnosis for fulfilment of nr-axSpA criteria was 30% and 40% for mNY criteria. Patients with r-axSpA/AS were older, more often men, and had longer disease duration, more uveitis, and worse spinal mobility than nr-axSpA patients, who had more enthesitis and dactylitis. CONCLUSION: We found an overall good concordance between clinical axSpA diagnoses and classification criteria fulfilment, with 83% fulfilling ASAS axSpA and/or mNY criteria. Regarding axSpA subtypes, the concordance was weaker, and although the ICD-10 code for AS correctly identified patients meeting mNY criteria in 71% of cases, one-third of mNY-positive patients lacked an AS diagnosis. Moreover, clinical u-axSpA diagnoses could not serve as a proxy to identify nr-axSpA, highlighting the importance of thorough classification in research on axSpA subtypes.

The effect of a tight control regime with monthly follow-up on remission rates and reported pain in early rheumatoid arthritis.

OBJECTIVE: To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6 months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA). METHODS: In this single-centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2 years. RESULTS: The patients in the TC cohort had lower 28- joints disease activity score (DAS28) at three, six, 12 and 24 months, compared with the conventionally managed cohort, p ≤ 0.001. At 12 months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28 < 2.6) and at 24 months 68% versus 49% respectively, p < 0.05. The TC cohort reported less pain at three, six, 12 and 24 months, p < 0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24 months and with acceptable pain at 24 months. CONCLUSION: The intensive follow-up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.

Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis.

BACKGROUND: Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. METHODS: Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). RESULTS: Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. CONCLUSION: Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.

Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden.

OBJECTIVES: To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch. METHODS: Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors. RESULTS: In total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy. CONCLUSION: This large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.

Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision.

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.

Patients' Perceptions of Person-Centered Care in Early Rheumatoid Arthritis: A Qualitative Study.

OBJECTIVE: Most research on patient experiences of rheumatoid arthritis (RA) care is performed with patients who have established RA and less often with patients with early RA. Experiences of and expectations about health care may change over time, which is why the aim was to explore patients' perceptions of person-centered care (PCC) early in the RA disease course. METHODS: Thirty-one patients with early RA were interviewed in this qualitative study. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (1,2). The four constructs, prerequisites, care environment, person-centered processes, and person-centered outcomes, constituted the four categories in the deductive part of the study. An inductive analysis generated 11 subcategories exploring the content of PCC. RESULTS: For patients with early RA, PCC was described in terms of 1) prerequisites including being treated with respect, meeting dedicated health care professionals, and meeting professional competence; 2) care environment including having access to a multidisciplinary team, having access to health care, and encountering a supportive organization; 3) person-centered processes including being listened to, being supported, and being involved in decision-making; and 4) person-centered outcomes including being satisfied with received health care and achieving optimal health. CONCLUSION: Genuine PCC is important for patients early in the RA disease course, supporting the implementation of a person-centered approach during all stages in the health care system. This study contributes to information about how to further develop person-centeredness in rheumatology care.

Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population: a nationwide Swedish cohort study.

OBJECTIVES: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies. METHODS: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression. RESULTS: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited. CONCLUSIONS: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.

Chronic Pain and Assessment of Pain Sensitivity in Patients With Axial Spondyloarthritis: Results From the SPARTAKUS Cohort.

OBJECTIVE: To study differences in pain reports between patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA), and to assess how pain sensitivity measures associate with disease and health outcomes. METHODS: Consecutive patients with axial SpA (axSpA) were enrolled in the population-based SPARTAKUS cohort (2015-2017) and classified as AS (n = 120) or nr-axSpA (n = 55). Pain was assessed with questionnaires (intensity/duration/distribution) and computerized cuff pressure algometry to measure pain sensitivity (pain threshold/pain tolerance/temporal summation of pain). Linear regression models were used to compare pain measures between patients with AS and nr-axSpA, and to assess associations between pain sensitivity measures and disease and health outcomes. RESULTS: Of 175 patients with axSpA, 43% reported chronic widespread pain, with no significant differences in any questionnaire-derived or algometry-assessed pain measures between patients with AS and nr-axSpA. Lower pain tolerance was associated with longer symptom duration, worse Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Metrology Index (BASMI), more pain regions, unacceptable pain, worse Maastricht AS Enthesitis Score (MASES), fatigue, anxiety, and health-related quality of life. Further, lower pain threshold was associated with worse ASDAS-CRP and MASES, whereas higher temporal summation was associated with longer symptom duration, unacceptable pain, and worse BASMI. CONCLUSION: Chronic pain is common in axSpA, with no observed differences in any pain measures between patients with AS and nr-axSpA. Further, higher pain sensitivity is associated with having worse disease and health outcomes. The results indicate that patients with AS and nr-axSpA, in line with most clinical characteristics, have a similar pain burden, and they highlight large unmet needs regarding individualized pain management, regardless of axSpA subgroup.

What do patients prefer? A multinational, longitudinal, qualitative study on patient-preferred treatment outcomes in early rheumatoid arthritis.

OBJECTIVES: To explore treatment outcomes preferred by patients with early rheumatoid arthritis (RA) and how these change throughout the early disease stage across three European countries. METHODS: A longitudinal, qualitative, multicentre study was conducted in Belgium, the Netherlands and Sweden. 80 patients with early RA were individually interviewed 3-9 months after treatment initiation and 51 of them participated again in either a focus group or an individual interview 12-21 months after treatment initiation. Data were first analysed by country, following the Qualitative Analysis Guide of Leuven (QUAGOL). Thereafter, a meta-synthesis, inspired by the principles of meta-ethnography and the QUAGOL, was performed, involving the local research teams. RESULTS: The meta-synthesis revealed 11 subthemes from which four main themes were identified: disease control, physical performance, self-accomplishment and well-being. 'A normal life despite RA' was an overarching patient-preferred outcome across countries. Belgian, Dutch and Swedish patients showed many similarities in terms of which outcomes they preferred throughout the early stage of RA. Some outcome preferences (eg, relief of fatigue and no side effects) developed differently over time across countries. CONCLUSIONS: This study on patient-preferred outcomes in early RA revealed that patients essentially want to live a normal life despite RA. Our findings help to understand what really matters to patients and provide specific insights into the early stage of RA, which should be addressed by clinicians of different disciplines from the start of treatment onwards.

"Mastering a New Life Situation" - Patients' Preferences of Treatment Outcomes in Early Rheumatoid Arthritis - A Longitudinal Qualitative Study.

PURPOSE: To explore patients' preferred treatment outcomes during their first two years with rheumatoid arthritis (RA). PATIENTS AND METHODS: A qualitative, longitudinal, multicenter study with interviews at two time points was performed in Sweden. Individual interviews were conducted at time point 1 with 31 patients with RA, defined as disease duration of ≤1 year and treatment for 3-7 months. Seven focus group interviews and five individual interviews were conducted at time point 2 with 22 patients 12-20 months after treatment initiation. The interviews were analyzed using the Qualitative Analysis Guide of Leuven. A core category with four related concepts emerged. RESULTS: The core finding of patient-preferred treatment outcomes was "mastering a new life situation". Patients preferred to experience control of the disease by controlling the symptoms and by experiencing absence of disease. To experience autonomy by regaining former activity level, experiencing independence, and being empowered was another preferred outcome. Patients preferred to regain identity through being able to participate, experience well-being, and regain former self-image. To experience joy in everyday life through vitality and believing in the future was another preferred outcome. Patients' preferences developed over time from the acute phase of controlling the symptoms and wanting to return to the life they lived prior to diagnosis, to a more preventive way of self-management and empowerment to master the new life situation. CONCLUSION: The patients' preferred treatment outcomes during the first two years with RA were to master their new life situation and changed from a preference to return to a life lived prior disease onset, to a preference of living with quality of life, despite RA. This study increases the understanding of patients' preferred treatment outcomes in the early disease course and can be a foundation for tailoring interventions to be more person-centered and to improve long-term treatment outcomes.

Elevated faecal calprotectin is linked to worse disease status in axial spondyloarthritis: results from the SPARTAKUS cohort.

OBJECTIVES: To examine faecal calprotectin (F-calprotectin) levels and presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and their associations with disease subtype and current status in axial SpA (axSpA). METHODS: F-calprotectin and ASCA in serum were compared between consecutive patients with a clinical axSpA diagnosis, classified as non-radiographic axSpA (nr-axSpA; n = 40) or AS (n = 90), and with healthy controls (n = 35). Furthermore, standard axSpA outcome measures were compared between axSpA patients (nr-axSpA and AS combined) with elevated vs normal F-calprotectin, ASCA IgA and IgG, respectively. RESULTS: Elevated F-calprotectin (⩾50 mg/kg) was observed in 27% of nr-axSpA patients, 38% of AS patients and 6% of controls. F-calprotectin was significantly higher in AS vs nr-axSpA [AS: geometric mean 41 (95% CI 32, 54) mg/kg; nr-axSpA: 24 (95% CI 16, 38) mg/kg; P = 0.037], and in each axSpA subtype vs controls. Overall, worse disease activity and physical function scores were observed among axSpA patients with elevated vs normal F-calprotectin levels, with significant differences regarding patient's visual analogue scale for global health, ASDAS using CRP, and BASFI (adjusted for age, sex, NSAID use, anti-rheumatic treatments, and CRP). ASCA titres and seropositivity (⩾10 U/ml) were similar in nr-axSpA (IgA/IgG-seropositivity: 8%/26%) and AS (7%/28%), and clinical outcome measures did not differ between patients with elevated vs normal ASCA IgA or IgG, respectively. Compared with controls (IgA/IgG-seropositivity: 0%/17%), ASCA IgA was significantly higher in both axSpA subtypes, and IgG was significantly higher in the AS group. CONCLUSION: In patients with axSpA, gut inflammation measured by elevated F-calprotectin is associated with worse disease activity and physical function, and may be a marker of more severe disease.

Uptake of rheumatology biosimilars in the absence of forced switching.

BACKGROUND: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching. RESEARCH DESIGN AND METHODS: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima® and Inflectra®) and etanercept (Benepali®) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naïve patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type. RESULTS: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9 months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s). CONCLUSIONS: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.

Prevalence of chronic widespread pain in a population-based cohort of patients with spondyloarthritis - a cross-sectional study.

BACKGROUND: Chronic pain, regional or widespread, is a frequent and multidimensional symptom in arthritis. There is still limited information on chronic pain in spondyloarthritis, which is important to recognize for adequate diagnosis and treatment. Our objective was to study differences in prevalence of chronic widespread pain in two spondyloarthritis subgroups: ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA). METHODS: A population-based postal survey involving questions on the duration, distribution, and intensity of pain was answered by 940 patients with AS (ICD-10 M45.9) or USpA (ICD-10 M46.1-0, M46.8-9). The patients were categorized as having chronic widespread pain, chronic regional pain, or no chronic pain, and prevalence estimates for the pain groups were calculated, including age- and sex-adjusted prevalence. RESULTS: The prevalence of chronic widespread pain was 45.3% in AS vs. 49.3% in USpA, and that of chronic regional pain was 17.7% vs. 21.9% (p = 0.033). More women than men reported having chronic widespread pain (54.1% vs. 41.2%, p ≤ 0.001), while the sex distribution for chronic regional pain was equal. Reports of pain intensity were equal in AS and USpA, with no significant difference in pain intensity between women and men who had chronic regional pain or chronic widespread pain. In the multiple logistic regression analysis, chronic widespread pain was associated to female sex, being an ever-smoker, and having a higher body mass index, controlled for SpA subgroup and disease duration. CONCLUSIONS: The prevalence of chronic widespread pain in patients with AS and USpA is high, and with a female predominance, but with no difference in pain intensity between women and men. Chronic pain can complicate the clinical evaluation in patients with SpA, and highlights the need for a thorough clinical examination, including evaluation of inflammation and an accurate pain analysis, to individualize non-pharmacological and pharmacological treatment decisions.

The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical.

BACKGROUND: Rheumatoid arthritis (RA) consists of two syndromes, one autoantibody-positive and one autoantibody-negative. Existing data on the relation between age of onset and prevalence of autoantibodies were conflicting. Therefore this multicohort study assessed the age of onset in relation to the presence of autoantibodies. The association with characteristics of the anti-citrullinated protein antibodies (ACPA) response was also explored. METHODS: The 1987 criteria-positive RA patients included in the Leiden EAC, BARFOT, ESPOIR, Umeå and Lund cohorts (n = 3321) were studied at presentation for age of onset and the presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies. Logistic regression analyses were performed; effect sizes were summarized in inverse-weighted meta-analyses. Within ACPA-positive RA, ACPA level was studied in all cohorts; ACPA isotypes, ACPA fine specificity and ACPA avidity index and clinical characteristics were studied in the Leiden EAC. RESULTS: From the age of 50 onward, the proportion of ACPA-negative RA patients increased with age in the five cohorts. Similar observations were made for RF and anti-CarP. The composition of the ACPA response did not change with increasing age of onset with respect to titer, isotype distribution, fine specificity and avidity index. With increasing age of onset, RA patients smoked less often, had higher acute phase reactants and more often had a sub(acute) symptom onset. CONCLUSIONS: Data of five cohorts revealed that with older age of onset ACPA-negative RA is more frequent than ACPA-positive RA, while characteristics of ACPA-positive RA as judged by the composition of the ACPA response appeared not age dependent. Further biologic studies are needed to characterize the pathogenesis of ACPA-negative polyarthritis at older age and to promote personalized treatment decisions in ACPA-negative patients in daily practice.