Male patients with inflammatory joint diseases are less likely than controls to be childless: results from a Norwegian population-based cohort study of 10 865 patients.

OBJECTIVES: To investigate the number of children per man and the proportion of childless men as a proxy of fertility in a national cohort of men with inflammatory joint diseases (IJDs), compared with matched controls from the general population. METHODS: This is a nationwide, population-based retrospective cohort study. Male patients with IJDs (n = 10 865) in the Norwegian Arthritis Registry were individually matched 1:5 on birth year and county of residence with men without IJDs obtained from the National Population Register (n = 54 325). Birth data were obtained from the Medical Birth Registry of Norway. We compared the mean number of children per man and the proportion of childless men and analysed the impact of age and year of diagnosis. RESULTS: The mean number of children per man in the patient group was 1.80 versus 1.69 in the comparison group (p <0.001), and 21% of the patients in the patient group were childless versus 27% in the comparison group (p <0.001). The finding of less childlessness and higher number of children per man remained consistent across age at diagnosis, except for those diagnosed at age 0-19 years. The difference in childlessness was most pronounced for men diagnosed after year 2000, especially when diagnosed at 30-39 years of age (22% vs 32%, p<0.001). CONCLUSION: In this large cohort study we found that patients with IJD have a higher number of children and are less likely to be childless compared with controls. Factors associated with developing or having an IJD might influence fertility and this requires further investigation.

Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial.

OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308.

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.

BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments. TRIAL REGISTRATION NUMBER: NCT01491815.

Exploring the impact of the national tender system on the use of costly drugs treating rheumatoid arthritis patients in ten rheumatology centers in Norway (2010-2019).

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. METHOD: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. RESULT: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. CONCLUSION: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.

Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study.

OBJECTIVES: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. METHODS: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. RESULTS: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. CONCLUSIONS: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010-2019 - a country with a national tender system for prescription of costly drugs.

BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful.

Apparent diffusion coefficient values in Modic changes - interobserver reproducibility and relation to Modic type.

BACKGROUND: Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. METHODS: We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p < 0.001 to 0.02): MC-ADC (10- 6 mm2/s) 1201/796/576, MC-ADC% 36/21/14, and MC-ADC-ratio 5.9/4.2/3.1. MC-ADC and MC-ADC% had moderate to high ability to discriminate between the MC type groups (AUC 0.73-0.91). MC-ADC-ratio had low to moderate ability (AUC 0.67-0.85). At L4-S1, widest/narrowest LoA were for MC-ADC 20 ± 407/12 ± 254, MC-ADC% 1.6 ± 18.8/1.4 ± 10.4, and MC-ADC-ratio 0.3 ± 4.3/0.2 ± 3.9. Difference between observers > 50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17-20%). CONCLUSIONS: The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial.

Importance: Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective: To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions: Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures: The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results: Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance: Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01881308.

Increasing incidence and prevalence of ANCA-associated vasculitis in Northern Norway.

OBJECTIVE: ANCA-associated vasculitides (AAV) have increased in prevalence since the 1980s. We aimed to investigate the incidence and prevalence of AAV during a 15-year period from 1999 to 2013 in Northern Norway, looking for variations during this period. METHODS: Patient records were retrieved from The Northern Norwegian Vasculitis Registry; in addition we searched all regional hospital databases. Patients diagnosed with AAV from 1999 through to 2013 were included. For prevalence data, patients residing in the area, but with AAV diagnosis prior to 1999, were also included. The diagnosis of AAV was based on the European Medicines Agency algorithm. RESULTS: We identified 140 cases; 88 were classified as granulomatosis with polyangiitis (GPA), 37 as microscopic polyangiitis (MPA) and 15 as eosinophilic granulomatosis with polyangiitis (EGPA). Adult (age ≥15 years) annual incidence rates per million were as follows: for GPA 15.6 (95% CI: 12.5, 19.2), MPA 6.5 (95% CI: 4.6, 9.0), EGPA 2.7 (95% CI: 1.5, 4.5) and overall AAV 24.7 (95% CI: 20.8, 29.2). Incidences of MPA and overall AAV showed an increasing trend (P < 0.05). Adult point prevalence rates per million in 2013 were 261 (95% CI: 213, 316) for GPA, 58.2 (95% CI: 36.9, 87.3) for MPA, 32.9 (95% CI: 17.5, 56.3) for EGPA and 351 (95% CI: 296, 416) for overall AAV. CONCLUSION: The incidence rate of GPA and the prevalence rates of GPA and EGPA are currently the highest reported. MPA increased significantly from a prior low incidence. The overall AAV annual incidence and prevalence are still increasing.

Obesity Increases Disease Activity of Norwegian Patients with Axial Spondyloarthritis: Results from the European Map of Axial Spondyloarthritis Survey.

OBJECTIVE: To investigate the prevalence of overweight and obesity, as well as the association between body mass index (BMI) and disease activity in patients with axial spondyloarthritis (axSpA). METHODS: Norwegian axSpA patients from the European Map of Axial Spondyloarthritis (EMAS) survey were included in this analysis. Sociodemographic, anthropomorphic, and disease-related variables (HLA-B27, comorbidities, BASDAI, and self-reported spinal stiffness) were reported. Patients were categorized into under/normal weight (BMI < 25 kg/m2), overweight (BMI ≥ 25 to < 30 kg/m2), and obese (≥ 30 kg/m2). RESULTS: Of the 509 participants in the EMAS survey, 35% were categorized as under/normal weight, 39% overweight, and 26% obese. Compared to under/normal-weight patients, overweight patients had significantly higher degree of spinal stiffness (mean (SD) 7.91 ± 2.02 vs 7.48 (2.15) and number of comorbidities (2.45 ± 2.11, vs 1.94), both p < 0.001. Obese patients had significantly higher disease activity (BASDAI mean (SD) 5.87 ± 1.78 vs 4.99 ± 2.08, p < 0.001), degree of spinal stiffness (8.18 ± 2.03 vs 7.48 ± 2.15, p = 0.006), and number of comorbidities (3.43 ± 2.43 vs 1.94. ± .38, p < 0.001) than under/normal weight patients. After adjusting for gender and age, obesity proved to be independently associated with disease activity. CONCLUSION: Obesity was associated with higher reported BASDAI score, and being overweight or obese was associated with a higher degree of spinal stiffness and number of comorbidities compared to under/normal weight respondents. The results highlight the serious impact of obesity on health status, and obesity should therefore be considered as a modifiable risk factor for disease activity within the disease management of axSpA.

The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial.

BACKGROUND: Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes. METHODS/DESIGN: The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18-65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients' clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes. DISCUSSION: Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes. The study is registered at ClinicalTrials.gov under the identifier NCT03704363 . The EudraCT Number: 2017-004861-29.

Health-related quality of life in patients with psoriatic and rheumatoid arthritis: data from the prospective multicentre NOR-DMARD study compared with Norwegian general population controls.

OBJECTIVES: To compare (1) Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), scale scores and Short Form-6 dimensions (SF-6D) between patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) and Norwegian general population controls and (2) improvements in these measures between patients with RA and PsA. METHODS: Analyses of covariance were performed to compare SF-36 measures between first-time enrolled patients with RA (n=3898) and PsA (n=1515) from the prospective observational multicentre NORwegian-Disease Modifying Anti-Rheumatic Drug study (6 months follow-up) and general population controls (n=2323). RESULTS: In age and gender-adjusted analyses, patients with PsA compared with patients with RA had similar PCS, MCS and SF-6D (p≥0.14), worse vitality and general health, but better physical functioning at 0/6 months (p≤0.03). With additional 28-joint disease activity scores adjustment as a proxy for joint inflammation, PCS, most scale scores and SF-6D were worse in patients with PsA than patients with RA at 0/3/6 months (p≤0.01). PCS was more impaired than MCS both in RA and PsA compared with general population controls (p≤0.001). Mean 3-month and 6-month improvements after disease-modifying anti-rheumatic drug treatment were larger in patients with RA than patients with PsA for bodily pain, vitality and mental health (p≤0.02). CONCLUSIONS: Health-related quality of life was overall similar in patients with RA and patients with PsA-with a tendency to worse scores in PsA-and worse compared with Norwegian general population controls.

First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach.

OBJECTIVES: To develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA). METHODS: Patients were included in one of two cohorts from 2010 to June 2013: disease-modifying antirheumatic drug naïve early RA or established RA starting/switching biologics. An extensive US examination was performed by experienced sonographers using a validated grey-scale (GSUS) and power Doppler (PDUS) semiquantitative scoring system with scores 0-3 for both GSUS and PDUS in 36 joints and four tendons. We performed factor analysis in the early RA US data and selected candidate joint/tendon sets based on these results. The proportion of information in the total US scores retained in these candidate sets was assessed by R(2) from linear regression analysis. Finally, the candidate sets and previously proposed joint scores were tested in the established RA cohort, and we also evaluated the sensitivity to change with standardised response means. RESULTS: 227 patients with early RA and 212 patients with established RA were included. We identified two candidate sets of joints/tendons: candidate set A consisted of seven joints/two tendons (meatacarpophalangeal 1 (MCP1), MCP2, proximal interphalangeal 3, radiocarpal, elbow, metatarsophalangeal 1 (MTP1), MTP2, tibialis posterior tendon, extensor carpi ulnaris tendon) and set B of nine joints/two tendons (MCP5 and MTP5 added to set A). Unilateral reduced scores retained 78%-85% of the information in total score, while bilateral reduced scores retained 89%-93%, and both sets performed better than previously proposed reduced joint scores, and similar or slightly better regarding sensitivity to change. CONCLUSIONS: The reduced GSUS and PDUS scores retained most of the information from the total score and performed well in a validation cohort of established RA. TRIAL REGISTATION NUMBER: NCT01205854, ACTRN12610000284066.

Comparative Effectiveness and Persistence of SB4 and Reference Etanercept in Patients With Psoriatic Arthritis in Norway.

OBJECTIVE: We aim to compare drug effectiveness and persistence between the reference etanercept (ETN) and ETN biosimilar SB4 in patients with psoriatic arthritis (PsA) naive to ETN and to investigate drug effectiveness and persistence in those undergoing a mandatory nonmedical switch from ETN to SB4. METHODS: We used a retrospective comparative database study including 1,138 patients with PsA treated with ETN or SB4 (years 1999-2021) in Norway. Disease activity score in 28 joints (DAS28) and drug persistence were compared between unmatched ETN (n = 644) and SB4 (n = 252) cohorts and in matched analyses (n = 144, both cohorts) at baseline using a propensity score (PS) to adjust for confounders. Drug persistence was analyzed with the Kaplan-Meier method. RESULTS: In unmatched analyses, difference in change from baseline between ETN (n = 140) and SB4 (n = 132) for DAS28 at one year was mean 0.67 (95% confidence interval [CI] 0.38-0.96) in favor of ETN. In PS-matched analyses, the difference in change from baseline between ETN (n = 54) and SB4 (n = 54) was mean 0.09 (95% CI -0.33 to 0.50), and the mean difference assessed with an analysis of covariance model was 0.01 (95% CI -0.38 to 0.40), both within predefined equivalence margin (±0.6). Drug persistence at one year was mean 0.75 (95% CI 0.71-0.78) for ETN, mean 0.58 (95% CI 0.51-0.63) for SB4, hazard ratio (HR) 2.45 (95% CI 2.02-2.97) in unmatched analysis, and mean 0.55 (95% CI 0.46-0.63) for ETN, mean 0.60 (95% CI 0.51-0.67) for SB4, HR 1.29 (95%CI 0.94-1.76) in PS-matched cohorts. CONCLUSION: At one year, outcomes for PsA disease activity and drug persistence were comparable for patients treated with either ETN or SB4. In patients undergoing a mandatory nonmedical switch from ETN to SB4, drug effectiveness was maintained during a two-year period.

Decreasing incidence of cervical spine fractures in patients with ankylosing spondylitis: a population-based study in Southeast Norway.

BACKGROUND CONTEXT: Individuals diagnosed with ankylosing spondylitis (AS) face an increased risk of spine fractures, specifically cervical spine fractures (CS-Fxs). In the past two decades, biological disease-modifying antirheumatic drugs (bDMARDs) have provided considerable relief from pain and an enhanced sense of wellbeing for a large segment of AS patients. Despite these improvements, it remains unclear whether extended use of bDMARDs can indeed reduce the risk of spine fractures. PURPOSE: In this study, we aimed to investigate the evolving patterns and epidemiology of traumatic CS-Fxs in both AS and non-AS populations. We hypothesized that the risk of CS-Fxs among AS patients would show a decreasing trend over time, while the risk among non-AS patients would remain constant. STUDY DESIGN/SETTING: Retrospective cohort study based on a prospective database. PATIENT SAMPLE: A total of 3,598 consecutive patients with CS-Fxs were treated at Oslo University Hospital over an 8-year period. OUTCOME MEASURES: CS-Fxs in AS patients were contrasted with non-AS-related CS-Fxs in terms of temporal trends, age, sex, injury mechanism, associated cervical spinal cord injury (cSCI), need for surgical fixation, and 30-day mortality. METHODS: Data regarding all CS-Fxs diagnosed between 2015 and 2022 were extracted from the Southeast Norway population-based quality control database for traumatic CS-Fxs. Categorical data were summarized using frequencies, and continuous data were summarized using medians. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-squared test and Fischer exact test were used to compare categorical variables. To investigate the trend in the incidence of fractures, two different Poisson models were fitted with the number of non-AS and AS fractures as dependent variables and the year as the explanatory variable. RESULTS: Over an eight-year period, we registered 3,622 CS-Fxs in 3598 patients, with AS patients accounting for 125 of these fractures. Relative to their non-AS counterparts, AS patients presented a 9-fold and 8-fold higher risk of initial and subsequent CS-Fxs, respectively. We observed a declining trend in AS-related CS-Fxs with an annual linear decrease of 8.4% (p=.026), whereas non-AS-related CS-Fxs showed an annual linear increase of 3.7% (p<.001). AS patients sustaining CS-Fxs were typically older (median age 70 vs. 63 years), predominantly male (89% vs. 67%), and more frequently experienced injuries due to falls (82% vs. 57%). They also exhibited a higher prevalence of subaxial CS-Fxs (91% vs. 62%), fewer C0-C2 CS-Fxs (14% vs. 44%), a higher rate of associated cSCI (21% vs. 11%), and a greater tendency for surgical fixation (66% vs. 21%). We observed a 30-day mortality rate of 11% in AS patients and 5.4% in non-AS patients (p=.005). CONCLUSIONS: The results of this study confirm the elevated risk of CS-Fxs among AS patients, although this risk appears to show a decreasing trend. The most plausible explanation for this risk reduction is the widespread application of bDMARDs.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. METHODS: In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. FINDINGS: Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). INTERPRETATION: Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. FUNDING: Research Council of Norway and South-Eastern Norway Regional Health Authority.

Epidemiology of spondyloarthritis: a review.

The classification of Spondyloarthritis (SpA) has been revised with the introduction of the ASAS classification criteria. Although this has best been described in ankylosing spondylitis and psoriatic arthritis, there are population studies evaluating the epidemiology of the different subgroups of SpA. In this paper, we present data on the incidence and prevalence of the subgroups of SpA in different populations, and point to data indicating how the introduction of new classification criteria, with the altered perception of the SpA entity, might impact on the epidemiology.

Effectiveness and Persistence in SB4- and Reference Etanercept-Treated Rheumatoid Arthritis Patients in Ordinary Clinical Practice in Norway.

OBJECTIVE: Biosimilars represent cost-effective alternatives to reference biologic disease-modifying antirheumatic drugs. Our objective was to compare drug effectiveness and drug persistence in the treatment of rheumatoid arthritis (RA), assessing the etanercept biosimilar SB4 in efficacy and safety compared with reference etanercept in a Phase III, randomized controlled trial. We applied EULAR Points to Consider for Comparative Effectiveness Research in a retrospective database study of etanercept and SB4 in patients treated in clinical practice in Norway. METHODS: Patients with RA (n = 1,455) treated with etanercept or SB4 between 2010 and 2018 at 5 centers in Norway with ≥1 year of follow-up were included. Disease outcomes (Disease Activity Score in 28 joints [DAS28] at week 52) and drug persistence were compared between unmatched etanercept (n = 575) and SB4 (n = 299) cohorts and matched analyses (n = 172, both cohorts) using propensity score (PS) matching to adjust for confounders. RESULTS: In unmatched analyses, the difference in change from baseline between etanercept (n = 221) and SB4 (n = 106) for DAS28 at week 52 was mean -0.02 (95% confidence interval [95% CI] -0.32, 0.27), demonstrating equivalence by the predetermined equivalence margin (±0.6). In PS-matched analyses, the difference between etanercept (n = 49) and SB4 (n = 49) was 0.03 (95% CI -0.46, 0.52), within the predefined equivalence margin. Persistence using the drug at week 52 was similar between etanercept (0.62 [95% CI 0.57, 0.65]) and SB4 (0.66 [95% CI 0.60, 0.71]) cohorts in the unmatched analysis; in PS-matched cohorts, persistence at week 52 was 0.52 (95% CI 0.44, 0.59) for etanercept and 0.68 (95% CI 0.61, 0.75) for SB4. CONCLUSION: Outcomes for disease status/drug persistence at week 52 were similar between patients with RA treated with etanercept or SB4.