Objectives To explore differences in health-related benefit status over 3 years, focusing on patterns of sick leave, work assessment allowance and disability benefits, between people who underwent rehabilitation and a matched control group.Design Prospective longitudinal multicentre cohort study using registry data over three consecutive years.Setting Secondary specialist rehabilitation services at 17 institutions across Norway.Participants Patients (n=2710), 42% with rheumatic and musculoskeletal diseases, aged 18–65 years referred for multidisciplinary rehabilitation at one of the participating institutions. They were propensity score matched with 37 760 controls from the national sick leave registry, based on sociodemographic factors and health-related benefit status.Intervention Multidisciplinary rehabilitation programmes, commonly lasting 3 weeks (range: 1 week to 6 months), tailored to individual needs.Primary outcome measures Days on health-related benefits (sick leave, work assessment allowance (WAA) and disability benefits) were quantified as lost workdays per month. Differences between groups were analysed using Generalised Estimating Equations across three consecutive years: the year before rehabilitation, the rehabilitation year and the year after rehabilitation.Results The rehabilitation group had more days on health-related benefits per month than controls throughout the observation period. During the rehabilitation year, they had on average 1.7 more days on sick leave (95 % CI 1.3 to 1.9), 2.3 more WAA days (95% CI 1.9 to 2.7) and 0.2 more days on disability benefits (95% CI 0.1 to 0.3). In the year after rehabilitation, they had 0.6 fewer days on sick leave (95% CI −0.8 to −0.3), but 3.7 more days on WAA (95% CI 3.1 to 4.2) and 0.6 more days on disability benefits (95% CI 0.4 to 0.8). Patterns were similar for the subgroup with rheumatic and musculoskeletal diseases.Conclusions People undergoing rehabilitation had more days on health-related benefits and a greater increase in long-term benefits, even after matching, indicating a higher disease and support burden than controls. Tailoring interventions and health-related benefits is an essential aspect of rehabilitation for people with complex work participation needs. Future research should include longer observation periods to explore long-term outcomes of rehabilitation.Trail registration number NCT03764982

OBJECTIVE:Proactive therapeutic drug monitoring (pTDM) intends to optimise tumour necrosis factor (TNF) inhibitor treatment through regular assessment of drug and antidrug antibody levels, enabling individualised dosing. However, health economic evidence for this strategy is limited. This study aims to evaluate the health benefits and costs of pTDM with infliximab compared with standard therapy. METHODS:Based on the 52-week randomised, controlled, open-label, multicentre Norwegian Drug Monitoring trial (NOR-DRUM) B trial, we estimated the cost-effectiveness of pTDM compared with standard infliximab maintenance therapy in patients with six different immune-mediated inflammatory diseases. For each patient (n=454), we estimated the 12-month healthcare costs, including pharmaceuticals, biochemical tests and other types of resource use. Reported in 2024 Euros, unit costs were based on market prices, diagnosis-related group cost weights and reimbursement schedules. We evaluated health outcomes with quality-adjusted life-years (QALYs), using the EuroQol five-dimension, three-level questionnaire (EQ-5D-3L) and Short Form six-dimension health utility measure (SF-6D). Indicator of cost-effectiveness was the incremental cost-effectiveness ratio, expressed as Euros/QALY, compared with an assumed cost-effectiveness threshold value of €23 755. We assessed sampling uncertainty using the non-parametric bootstrap. RESULTS:The mean 1-year cost per patient in the pTDM group was lower than in the standard therapy group, with a difference of €592 (95% CI -1304 to 107), while the QALYs based on EQ-5D-3L were 0.0018 higher (95% CI -0.0126 to 0.0165). Based on the bootstrap results, pTDM has a probability of 95% of being cost-effective. In explorative subgroup analyses, pTDM appeared cost-effective for some, but not all diagnoses. CONCLUSION:pTDM is very likely a cost-effective treatment strategy for patients with immune-mediated inflammatory diseases on infliximab maintenance therapy. TRIAL REGISTRATION NUMBER:NCT03074656.

Instrumental variable (IV) methods are widely used to address unmeasured confounding in observational studies but typically estimate the local average treatment effect (LATE) for compliers. If there exist effect modifying variables that also affect the choice of treatment, the LATE may have limited clinical relevance. To address this limitation, we propose a novel framework for estimating the conditional average treatment effect (CATE) for a categorical treatment variable in the presence of both observed confounding and effect-modifying variables in addition to valid IVs. Building on recent developments in data fusion between randomized trial and observational data, we combine IV estimators with estimators based on covariate adjustment. By making parametric assumptions about the residual unobserved confounding effect, we obtain a consistent estimator of the CATE with relatively high efficiency. In a simulation study with nonlinear effect modification and unobserved confounding, we show that our estimator outperforms competing IV and covariate-adjusted estimators in terms of mean squared error. We further illustrate the applicability of the method, utilizing it to compare tumor necrosis factor alpha inhibitors as the first line biologic treatment of rheumatoid arthritis conditional on age. The analysis identifies modest age-related heterogeneity in treatment effects and provides population-relevant clinically interpretable estimates. This work provides a general framework for combining instrumental and confounding information to estimate individualized causal effects when treatment effects are heterogeneous and there are more than two treatment alternatives.

OBJECTIVES:TNF-α inhibitors (TNFis) are effective biologic drugs for rheumatoid arthritis (RA), but their comparative efficacy is unclear due to limited direct comparisons. The objective of this work was to compare the efficacy of infliximab (INX), certolizumab pegol (CZP), etanercept (ETN), golimumab (GOM) and adalimumab (ADM) in achieving remission at 3 months in bio-naïve RA patients. METHODS:Using data from the NOR-DMARD study of adult RA patients in Norway starting a TNFi as their first biologic treatment, we employed a target trial emulation approach. TNFi selection is mainly determined by drug prices in annual national tenders, allowing us to use drug cost as an instrumental variable (IV). Applying a novel IV method, causal effects were estimated with remission at 3 months as the end point. Results were compared with standard regression analysis adjusted for baseline variables. RESULTS:The IV analysis suggested potential differences in efficacy among TNFis, with INX showing higher remission rates compared with CZP, and ETN performing better than GOM. However, confidence intervals were wide, and many comparisons were not statistically significant. Sensitivity analyses confirmed the overall direction of results. Regression analysis adjusting for observed confounders showed no substantial differences, underscoring the importance of addressing unobserved confounding effects. CONCLUSION:This hypothesis-generating study provides evidence that TNFis may not be equally effective. The uncertainty in the estimates highlights the need for a pragmatic randomized controlled trial to validate the findings. With decreasing costs of TNFis, such studies are increasingly feasible and critical to guide clinical decision-making.

OBJECTIVES:To determine how certolizumab pegol (CZP) dose and dose adjustments influence CZP plasma trough levels to facilitate therapeutic drug monitoring of CZP. METHODS:The effect of CZP dose and dose adjustments on CZP plasma trough levels was evaluated post hoc using longitudinal data from a 52-week randomized phase III trial (RAPID 1) and its open-label extension trial. Patients with active rheumatoid arthritis treated with methotrexate for ≥6 months were randomized to CZP 200 mg, 400 mg, or placebo every other week (EOW). Patients in the extension trial were initially treated with CZP 400 mg EOW, then reduced to 200 mg EOW after ≥6 months. RESULTS:Of 982 randomized patients, 846 patients entered the open-label extension trial. Median (interquartile range) plasma CZP concentrations after 12 weeks of treatment were 21.3 mg/L (14.7, 27.7) in the 200-mg group and 38.3 mg/L (29.2, 63.8) in the 400-mg group and increased from 18.3 (12.4, 26.5) to 43.4 (26.8, 63.3) mg/L after dose escalation from 200 to 400 mg EOW. Following CZP dose reduction from 400 mg to 200 mg, median CZP levels decreased from 36.1 (24.9, 49.0) to 17.2 (11.5, 23.1) mg/L. CONCLUSIONS:CZP plasma concentrations were influenced by both dose and dose adjustment in a predictable manner, with median plasma levels twice as high in the 400-mg group than in the 200-mg group, with a 2-fold increase after the dose increase from 200 to 400 mg. This facilitates the development of algorithms for therapeutic drug monitoring of CZP.

OBJECTIVES:The objective of this paper is to examine whether patients with newly diagnosed rheumatoid arthritis (RA) can discontinue prednisolone after short-term bridging therapy. METHODS:Patients naïve to disease-modifying antirheumatic drugs with recent-onset RA in the ARCTIC (Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen) trial were followed for 24 months, with initial methotrexate monotherapy and prednisolone bridging therapy (tapering doses from 15 mg to 0 over 7 weeks). We explored the proportion of patients successfully discontinuing prednisolone, defined as no prednisolone use after bridging therapy, and for at least 4 subsequent months. Discontinuation was assessed after cessation of bridging therapy at 2, 3, 6, 12, 20, and 24 months. Additionally, we examined how many patients used prednisolone continuously for ≥3 months. RESULTS:Of 230 patients, 227 started prednisolone bridging therapy and were included for analyses. At baseline, mean (SD) age was 52 (13.7) years, mean (SD) disease activity score was 3.47 (1.17), 62% patients were female, and 82% patients were anticitrullinated peptide antibody positive. After 7 weeks, 84% (191/227) had discontinued prednisolone, 89% (203/227) had discontinued at 3 months, and 95% (216/227) within 24 months. Five percent (11/227) used prednisolone at every visit. The median number of days (IQR) of prednisolone use during 2 years was 55 (48-90). Among those who discontinued after 7 weeks, 80% (152/191) did not restart prednisolone. Continuous use for at least 3 months was observed in 22%. CONCLUSIONS:In newly diagnosed patients with RA using bridging therapy when starting methotrexate, over 80% successfully discontinued prednisolone. This supports that tapering to discontinuation is achievable in most patients after short-term bridging with prednisolone, in line with current European Alliance of Associations for Rheumatology recommendations.

OBJECTIVES:This study aimed to determine whether novel follow-up regimen, remote monitoring, or patient-initiated care is noninferior to usual care in maintaining low disease activity, in patients with axial spondyloarthritis (axSpA). METHODS:This is a randomised, controlled, 3-armed, parallel-group, open-label, noninferiority trial. Patients with axSpA in low disease activity on stable treatment with tumour necrosis factor inhibitor were recruited from a Norwegian outpatient clinic. Patients were randomly allocated 1:1:1 to remote monitoring, patient-initiated care, or usual care (control group), with 18 months of follow-up. Primary outcome was mean probability of axSpA Disease Activity Score (ASDAS) of <2.1, compared between groups at 6, 12, and 18 months, with 15% noninferiority margin. Secondary outcomes included other measures of disease activity, physical function, patient satisfaction, change of medication, resource use, and adverse events. RESULTS:Of 243 patients enrolled patients, 235 completed the study (remote monitoring = 75, patient-initiated care = 79, usual care = 81). At the 6-month, 12-month, and 18-month assessments, 90% or more patients in all 3 groups had ASDAS of <2.1. The estimated difference of probability of ASDAS < 2.1 was as follows: usual care vs remote monitoring, -4.1% (97.5% CI, -9.9% to 1.8%); usual care vs patient-initiated care, -1.1% (97.5% CI, -7.2% to 4.9%); and remote monitoring vs patient-initiated care, 2.9% (95% CI, -1.5% to 7.4%). Health providers' resource use was lowest in patient-initiated care; other secondary outcomes were comparable. CONCLUSIONS:In patients with axSpA in low disease activity and on stable treatment with tumour necrosis factor inhibitor, follow-up with remote monitoring or patient-initiated care was noninferior to usual care in maintaining low disease activity, supporting the implementation of novel follow-up strategies.

IntroductionAchieving remission is a critical therapeutic goal in the management of rheumatoid arthritis (RA). Despite methotrexate being the cornerstone of early RA treatment, a significant proportion of patients fail to achieve remission. This study aims to predict 6-month non-remission in 222 disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients initiating methotrexate monotherapy, using baseline patient characteristics from the ARCTIC trial.MethodsMachine learning models were developed utilizing twenty-one baseline demographic, clinical and laboratory features to predict non-remission according to ACR/EULAR Boolean, SDAI and CDAI criteria. The model employed a super learner algorithm that combine three base algorithms of elastic net, random forest and support vector machine. The model performance was evaluated through five independent unseen tests with nested 5-fold cross-validation. The predictive power of each feature was assessed using a composite measure derived from individual algorithm estimates.ResultsThe model demonstrated a mean AUC-ROC of 0.75-0.76, with mean sensitivity of 0.77-0.81, precision (also referred to as Positive Predictive Value) of 0.77-0.79 and specificity of 0.63-0.66 across the criteria. Predictive power analysis of each feature identified the baseline Rheumatoid Arthritis Impact of Disease (RAID) score as the strongest predictor of non-remission. A simplified model using RAID score alone demonstrated comparable performance to the full-feature model.ConclusionThese findings highlight the potential utility of baseline RAID score-based model as an effective tool for early identification of patients at risk of non-remission in clinical practise.

Wrist inflammation is common in patients with rheumatoid arthritis (RA), and thus there is room for debate on which joints to include in an ultrasound-based scoring of wrist synovitis in RA. This study aimed to identify the most treatment-sensitive major wrist joint, and assess potential differences between patients with early and established RA. This post-hoc study analysed data from two independent cohorts, the ARCTIC trial (early RA) and the ULTRABIT study (established RA), with ultrasound-based semi-quantitative scoring of 36 joints and four tendons, including the radio-carpal (RC), inter-carpal (IC), and radio-ulnar (RU) joints of the wrists. Each joint was explored separately, along with the maximum score from two (RC, IC) or three (RC, IC, RU) joints, and the sum score of two (RC and IC, IC and RU, or RU and RC) or all three (RC, IC, and RU) joints. Sensitivity to change over 12 months for each wrist joint score was assessed using the standardised response mean (SRM). We included 208 and 162 patients with early and established RA, respectively. Patients with established RA showed a higher prevalence of wrist joint synovitis at baseline and 12 months than those with early RA. The maximum score of the three wrist joints was most sensitive to change in early RA; SRMs of the greyscale (GS) and power Doppler (PD) were -0.82 and -0.73, respectively. The SRM of the sum score of the three wrist joints was highest in established RA, with SRMs for GS of -0.56 and PD of -0.54, which were comparable to SRMs of maximum score of the three wrist joints. To assess changes in follow-up studies, ultrasound scoring should include all three major wrist joints in both early and established RA. The ARCTIC trial: ClinicalTrials.gov identifier: NCT01581294. Registered on 21 September 2010. ULTRABIT trial: Australian New Zealand Clinical Trials Registry; identifier: ACTRN12610000284066. Registered on 8 April 2010.

AIMS:A soft-tissue sparing posterior surgical approach (SPAIRE) for hip hemiarthroplasty after femoral neck fractures is hypothesized to provide better functional results than the standard direct lateral approach, while maintaining a low dislocation rate. The aim of this study was to compare rate of complications and functional results between these approaches in a clinical cohort. METHODS:Prospectively collected registry data on all femoral neck fracture cases treated with hemiarthroplasty between September 2018 and November 2022 in a single Norwegian hospital were analyzed grouped by SPAIRE versus direct lateral approach. Outcomes were prosthesis dislocation, surgical site infection, 30-day mortality, and tests of function three months postoperatively. Linear regression was used for continuous outcomes, and dichotomous outcomes were analyzed by logistic regression and contingency tables. RESULTS:Of 858 cases, 430 were operated using SPAIRE, and 428 using direct lateral approach. There were no group differences in prosthesis dislocation rate (SPAIRE 0.7 % vs direct lateral 0.9 %, p = 0.725), and no differences in surgical site infections or 30-day mortality. In the patients with three months follow-up (total n = 372; SPAIRE n = 192; direct lateral n = 180) the SPAIRE group had better functional outcomes; New Mobility Score: 6.1 vs 5.0 (difference 1.1, p < 0.001), New Mobility Score change from preoperative: -1.3 vs -1.8 (difference 0.5, p = 0.024), Short Physical Performance Battery: 7.3 vs. 5.9 (difference 1.4, p < 0.001), Walking speed: 0.8 vs 0.7 m/s (difference 0.1, p < 0.001). CONCLUSION:We found no differences in the rate of prosthesis dislocations, infections, or mortality between the SPAIRE and the direct lateral approach. Functional outcomes were better in patients operated with the SPAIRE approach.

Objective Our primary objectives are to assess whether intraarticular corticosteroid injections are superior to saline injections with regards to thumb base pain after 4 weeks, and to compare the efficacy of steroid injections, saline injections, and an occupational therapy intervention on thumb base pain after 12 weeks in people with painful inflammatory osteoarthritis (OA) of the first carpometacarpal (CMC-1) joint. Design In this three-armed, double-blind, randomized multicenter trial, 354 participants with painful inflammatory CMC-1 OA from six Norwegian hospitals are recruited. Participants are randomized 1:1:1 to intraarticular steroid or saline injections in the CMC-1 joint or a multimodal occupational therapy intervention. The primary outcomes are thumb base pain measured on a numeric rating scale (NRS, range: 0-10) after 4 weeks and 12 weeks. Key secondary outcomes include synovitis by Magnetic Resonance Imaging (MRI) after 4 weeks and hand function by the Measure of Activity Performance of the Hand (MAP-Hand) questionnaire after 12 and 24 weeks. Other secondary outcomes are synovitis by clinical examination and ultrasound, measures of pain, function, stiffness, and health-related quality of life, and direct and indirect costs. Adverse events are recorded at each visit. The duration of the randomized controlled trial is 24 weeks, followed by an 80-week open-label observational phase to investigate the long-term efficacy and safety of repeated steroid injections and the occupational therapy intervention. Conclusions The results from this trial will have important clinical implications and influence future guidelines on OA management of the CMC-1 joint. Clinical trial registration EU-CT 2023-505254-17-00, NCT06084364

Background: Novel follow-up strategies such as Remote Monitoring and Patient-initiated Care may allow for more targeted and efficient use of health-care resources compared to conventional prescheduled face-to-face outpatient visits. However, knowledge regarding the effectiveness of these strategies is scarce. This is the first randomized clinical trial assessing novel follow-up strategies, Remote Monitoring and Patient-initiated Care, versus Usual Care, in axial spondyloarthritis (axSpA). Objectives: To determine whether (i) Remote Monitoring or (ii) Patient-initiated Care for axSpA were non-inferior to (iii) Usual Care in maintaining low disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS) <2.1) over 18 months. Methods: ReMonit is a three-armed, single-center, parallel-group, randomized, controlled, open-label non-inferiority trial assessing patients with axSpA in low disease activity on stable treatment with a tumor necrosis factor inhibitor (TNFi). Patients were randomized 1:1:1 to Usual Care with face-to-face hospital visits every six months, Remote Monitoring with monthly digital reporting of patient-reported outcomes (PROs) and no prescheduled visits, or Patient-initiated Care with self-monitoring and no prescheduled visits during the 18-months follow-up. In Remote Monitoring, patients were contacted if the PROs exceeded a pre-defined value (Bath Ankylosing Disease Activity Index ≥4), and were offered a consultation. Patients in all groups could contact the study nurse and request a consultation. The primary endpoint was low disease activity (ASDAS <2.1) evaluated at three timepoints, at 6, 12, as well as 18 months for each patient. Secondary outcomes included other measures of disease activity (ASDAS continuous, C-reactive protein), physical function (Bath Ankylosing Spondylitis Functional Index), patient satisfaction with care, and number of consultations and telephone calls with a rheumatologist or a rheumatology nurse. Mixed effect logistic regression was used to estimate the group-specific marginal probability of ASDAS <2.1 across 6, 12 and 18 months. The non-inferiority of Remote Monitoring vs. Usual Care, and Patient-initiated Care vs. Usual Care was assessed for the between-group differences in the probability of ASDAS <2.1, using a family-wise error rate of 2.5% and a non-inferiority (NI) margin of 15%. If Patient-initiated Care was shown to be non-inferior to Usual Care, it was predefined to assess non-inferiority of Patient-initiated Care vs. Remote Monitoring [1]. ClinicalTrials.gov no. NCT06211322. Results: Of 346 screened patients, 242 were enrolled between September 2021 and June 2022 and randomly allocated to the 3 study arms (Usual Care: n=82, Remote Monitoring: n=79, Patient-initiated Care: n=81). The mean age was 44 years (SD 12), 182 (75%) were males, and mean ASDAS was 1.0 (SD 0.5) at baseline, with balanced study groups. No significant between group differences in ASDAS<2.1 were seen, and upper boundary of 95% CI was well below NI-margin (Figure 1). Both Remote Monitoring and Patient-initiated Care were deemed non-inferior to Usual Care, and Patient-initiated Care to Remote Monitoring. Secondary endpoints on disease activity and function were comparable (Figure 2). Patient satisfaction with care was similar across the three study arms at all timepoints with >90% reporting to be satisfied or very satisfied with the follow-up. The number of consultations were higher in Usual Care than in Remote Monitoring and Patient-initiated Care, but number of telephone calls was higher in Remote Monitoring than Usual Care and Patient Initiated Care (Figure 2). Conclusion: In this study, Remote Monitoring and Patient-initiated Care were both non-inferior to Usual Care in maintaining low disease activity in axial spondyloarthritis over an 18-month period. Patient-initiated Care was also non-inferior to Remote Monitoring. The results indicate that such follow-up strategies could be implemented in patients with axSpA in low disease activity, as an alternative to regular outpatient visits to optimize health care recourses. REFERENCES: [1] Berg et al. JMIR Res Protoc. 2023 Dec 27;12:e52872. Acknowledgements: NIL. Disclosure of Interests: Inger Jorid Berg Has received fees from Novartis in 2019 outside the submitted work, Joseph Sexton: None declared, Eirik Kristianslund: None declared, Anne Therese Tveter: None declared, Gunnstein Bakland From UCB, outside the submitted work, Laure Gossec grants or personal fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, Stada and UCB outside the submitted work, Espen A Haavardsholm speaker or consultant fees from Pfizer, AbbVie, UCB Pharma, Eli Lilly, Novartis, and Boehringer Ingelheim outside the submitted work, speaker or consultant fees from Pfizer, AbbVie, UCB Pharma, Eli Lilly, Novartis, and Boehringer Ingelheim outside the submitted work, Sarah Hakim: None declared, Gary J. Macfarlane: None declared, Ellen Moholt: None declared, Sella Aarrestad Provan speaker or consultant fees from Pfizer and Boehringer Ingelheim outside the submitted work, research grant from Boehringer Ingelheim outside the submitted work, Emil Eirik Kvernberg Thomassen: None declared, Annette de Thurah: None declared, Siri Lillegraven: None declared, Nina Osteras: None declared.

PURPOSE:Knowledge about factors associated with mortality after hip fracture is important both for analytical and clinical purposes. This study aimed to assess patient risk factors and commonly used composite scores for prediction of 1-year mortality in a large clinical cohort. METHODS:Hip fracture patient data were prospectively recorded in a local hospital database. Consecutive fractures from 2006 to 2020 were included, 6040 fractures in 5496 patients. Associations between 1-year mortality and different exposures were estimated using univariate and two multivariate logistic regression models. ROC analysis was used to compare the ability of the Nottingham Hip Fracture Score (NHFS), Age-adjusted Charlson Comorbidity Index (ACCI) the American Society of Anesthesiologists score (ASA) and the Orthopedic Frailty Score (OFS) to predict 1-year mortality. RESULTS:Females sustained 73.9% of the fractures. Total 1-year mortality was 24.8%. Patients with overweight and class 1 obesity had lower 1-year mortality rates than normal weight patients [overweight: adjusted OR 0.58 (0.45-0.77), class 1 obesity: adjusted OR 0.40 (0.21-0.75)]. Mortality was elevated in males (adjusted OR 2.04, 95% CI 1.76-2.36), and nursing home residents (adjusted OR 2.99, 95% CI 2.60-3.44). We found no significant association between waiting time before surgery and mortality. Models including ACCI (AUC 0.74), NHFS (AUC 0.75) and OFS (AUC 0.73) had a similar ability to predict 1-year mortality, while a model including ASA (AUC 0.71) had a significantly lower prediction ability than ACCI and NHFS. CONCLUSIONS:Sex, age, cognitive impairment, and residential status predicted 1-year mortality. The study found an apparent "obesity paradox", where overweight patients had a lower mortality rate than normal weight patients, but unmeasured confounding may have biased this analysis. ACCI and NHFS predicted mortality better than the combination of age, sex, and ASA.

ObjectiveTapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare-free survival and joint damage progression over three years.MethodsARCTIC REWIND was a multicenter open-label, noninferiority trial that included patients with RA in remission for >= 12 months taking stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary end points of the current study were flare-free survival and radiographic progression over three years. Flare-free survival was analyzed by Kaplan-Meier methods, flare rates were analyzed by Cox regression, and radiographic progression was analyzed by logistic mixed-effects models.ResultsOf 99 randomized patients, 92 received the allocated therapy, and 80 completed the three-year follow-up. The mean baseline Disease Activity Score based on the 44 joint count was 0.8, and conventional synthetic disease-modifying antirheumatic drug comedication was used by 90% of patients. After three years, 25% (95% confidence interval [CI] 13%-38%) remained flare free in the tapering TNFi group, compared to 85% (95% CI 70%-93%) in the stable group, and the corresponding hazard ratio for flare was 9.4 (95% CI 3.9-22.8, P < 0.0001). In the tapering group, 6 of 41 (15%) experienced radiographic progression, compared with 3 of 38 (8%) in the stable group (risk difference 6.7%, 95% CI -7.1% to 20.5%, P = 0.3). Adverse events occurred in 81% of the patients in the tapering group and 89% of the patients in the stable group.ConclusionIn contrast to those receiving stable TNFi treatment, a minority of patients with RA in remission tapering TNFi to withdrawal remained flare free over three years. There was no statistically significant difference in radiographic progression between the groups.

IntroductionQuality improvement in rehabilitation is needed due to unwarranted variations and suboptimal service coordination. Audit and feedback strategies are commonly used to improve healthcare quality, but evidence of their effectiveness in rehabilitation settings is limited.ObjectiveTo evaluate the impact of an audit and feedback strategy on rehabilitation quality, as measured by a set of quality indicators (QIs) specifically designed for rehabilitation.MethodsInterrupted time series analysis was conducted across 16 Norwegian institutions delivering specialized rehabilitation for long-term diseases. Patient-reported rehabilitation quality data was collected continuously before and after a provider feedback intervention, while provider-reported quality was measured once before and after the intervention. We compared 11 pre- and 9 post-intervention observations, each spanning 3 weeks, over a 15-months study period.ResultsThe analyses included 2,415 patients, with 1,444 (59.8%) pre-intervention and 971 (40.2%) post-intervention. Mixed model analyses revealed that the mean differences in patient-reported QIs between the pre- and post-intervention phase were small and statistically non-significant. The expected impact model, including a gradually higher quality after the feedback to institution managers and clinical team members, was not confirmed. We observed variations in service quality among institutions, also post-intervention. The lowest pass rates were observed for indicators addressing the follow-up, involvement of external services and next of kin.ConclusionsIn this multicentre study, the audit and feedback intervention did not lead to improvements in the quality of rehabilitation services, as measured by changes in QI pass rates covering health service structures, processes and patient outcomes. Clinical Trial RegistrationClinicalTrials.gov [NCT03764982].

Objective: Previous studies on the efficacy of methotrexate in people with hand osteoarthritis (OA) have shown conflicting results. The MERINO trial aims to investigate the efficacy and safety of methotrexate in people with painful inflammatory erosive hand OA. Design: In total 163 participants with erosive hand OA, synovitis by ultrasound, and finger joint pain of 40-80 mm on a visual analogue scale (VAS) will be recruited from a rheumatology outpatient clinic. Participants are randomized 1:1 to receive either encapsulated oral methotrexate 20 mg/week or placebo for 12 months in a doubleblind manner. The primary endpoint is VAS finger joint pain at 6 months. Key secondary outcomes are hand function by the Australian/Canadian hand index (AUSCAN) at 6 months and radiographic progression by the Verbruggen-Veys anatomical phase scoring system at 12 months. Other secondary endpoints include hand stiffness, disease activity, health-related quality of life, grip strength, clinical joint counts, synovitis by ultrasound and MRI, bone marrow lesions by MRI, cost-effectiveness, and symptoms in knees and hips. Adverse events will be recorded. The primary analysis will be performed on full analysis set. Conclusions: The findings of this trial will be clinically relevant for patients with erosive hand OA and may influence future treatment recommendations. Clinical trial registration: EU CT number: 2023-510523-30-00, NCT04579848.

Background As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi). Methods In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi. Findings Between December 17, 2021, and June 20, 2023, 456 infection-naive patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138-45,233) vs 36,341 IU/ml (11,887-53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176-54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naive patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494-50,211)) compared to the fourth dose (7304 IU/ml (3245-17,260), p < 0.0001). CD8 T cell responses remained stable following a fourth dose (median frequency of spike-specific cells 0.039% (IQR 0.010-0.14)), infection (0.058% (0.026-0.17)) and a fifth dose (0.058% (0.013-0.20). Interpretation In patients on TNFi with hybrid immunity, there was no immunological benefit of an updated fifth SARS-CoV-2 booster dose. Stable CD8 cellular responses following four doses indicate established protective immunity. Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).