OBJECTIVES:Ultra-low dose rituximab is an effective treatment in rheumatoid arthritis (RA). Subcutaneous (SC) administration may further facilitate rituximab treatment, reduce infection risk, and reduce costs. This study aimed to assess non-inferiority of SC versus intravenous (IV) rituximab regarding pharmacokinetic and -dynamic (PKPD) outcomes. METHODS:In this randomised, open-label, non-inferiority study, RA patients with stable low disease activity on ultra-low dose rituximab (500 mg or 200 mg every 6 months) were 1:1 randomised to receive rituximab 336 mg SC or 200 mg IV, stratified by previous rituximab dose. Primary outcome was non-inferiority of SC to IV rituximab, based on the estimated rituximab serum concentration area under the curve during the first 6 months (AUC0-6 months), with a non-inferiority margin of 0.8. AUCs were estimated using PK modelling. Secondary outcomes included change in DAS28-CRP compared to a NI-margin of 0.6. RESULTS:Thirty-five patients were randomised (17 IV, 18 SC). The geometric mean ratio for AUC0-6m was 0.99 (90%-CI 0.82 to 1.20), with minimal bias (mean predication error: IV 13.1 (1.86%); SC -3.40 (-0.47%)) but moderate random prediction error (root mean square error: IV 140 (19.8%); SC 142 (19.5%)) for the AUC estimates. Mean change in DAS28-CRP was non-inferior for SC rituximab (-0.39, 95%-CI -0.77 to -0.004). CONCLUSION:Our data suggest non-inferior pharmacokinetics for SC rituximab; however, this cannot be definitively concluded due to uncertainty of the AUC estimates. Nevertheless, based on PK/PD parameters, ultra-low dose SC rituximab could be an alternative for ultra-low dose IV rituximab.

Objectives:Rituximab (RTX) is an effective and safe treatment for rheumatoid arthritis (RA), but is associated with an increased risk of reactivation of hepatitis B virus (HBV) infection. Therefore, (inter)national guidelines recommend HBV screening prior to initiation of RTX treatment. However, the incidence of HBV in RA patients in nonendemic areas is expected to be very low, with known suboptimal screening adherence. This study aims to assess the added diagnostic value of routine serological HBV screening in RA patients initiating RTX. Methods:This retrospective single-centre cohort study included all patients with a clinical diagnosis of RA intending to initiate RTX between April 2012 and April 2024. Data on patient and disease characteristics, HBV screening results, and additional laboratory results were collected. Adherence to HBV screening, proportion of positive test results (hepatitis B surface antigen or core antibody positive), and incidence of HBV reactivation were assessed. Results:Of 975 included patients, 270 (28 %) were serologically screened for HBV. Six of those (2.2 %) had a positive screening result, of whom 3 eventually did not receive RTX. All 6 had a known HBV history or risk factor. No active HBV infections were observed after initiating RTX (mean follow-up 6.97 years), regardless of screening. Conclusions:Routine serological HBV screening identified very few previously unrecognised infections, and-in spite of screening adherence being low-no HBV reactivations occurred. Routine serological HBV screening, therefore, seems redundant in a low-risk population and should be reserved for patients with known risk factors.

Background It is currently unclear what the optimal treatment strategy is after failing an IL-6Ri in rheumatoid arthritis (RA), switching to another mode of action (MOA) DMARD, or cycling to a next IL-6Ri. We set out to compare the effectiveness of these strategies. Methods In this retrospective cohort study, RA patients who have ever used an IL-6Ri were included (termed “first IL-6Ri cohort”). Within this cohort, two subcohorts were developed: a cycle subcohort, comprising patients who received a second IL-6Ri and a (matched) switch subcohort, comprising patients who received another MOA b/tsDMARD. Effectiveness was measured as restricted mean drug survival time (RMST) over a 36-month period and DAS28-CRP scores, adjusted for baseline, after 3, 6 and 12 months. The cycle subcohort was compared to the first IL-6Ri cohort and the switch subcohort. Results 1,054 patients were included, of whom 134 and 267 in the cycle and switch subcohorts respectively. RMST of the cycle subcohort was lower than the first IL-6Ri cohort (-4.5 months (95% CI: -7.1 to -1.8)), but comparable to the switch subcohort (-2.1 months (95% CI: -5.3 to 1.2)). After 6 months, mean DAS28-CRP score of the cycle subcohort was higher compared to the first IL-6Ri cohort but comparable to the switch subcohort. Conclusions Effectiveness of a second IL-6Ri is lower compared to the first IL-6Ri, but comparable to other MOA switch options. Therefore, treatment choices after IL-6Ri failure in RA can be made based on other factors than drug MOA and may thus include a second IL-6Ri.

Objectives The Simple Erosion Narrowing Score (SENS) is a simplification of the Sharp/van der Heijde score (SHS). Previous studies found SENS and SHS to have very similar measurement properties, but suggest that SENS has a lower discriminative ability that may result in reduced power. Therefore, we aimed to quantify the effect of using SENS rather than SHS on the power to show between-group differences in radiographic progression. Methods Using data from two clinical trials in RA (DRESS and BeSt), SENS was derived from the SHS. Criterion validity of the SENS in relation to the SHS was assessed by calculating the Spearman correlation. The power of both scores to show a difference between groups was compared using bootstrapping to generate 10 000 replications of each study. Then, the number of replications with a significant difference in progression (using analysis of covariance adjusted for baseline scores) were compared. Results Correlations between SENS and SHS were all >0.9, indicating high criterion validity of SENS compared with SHS as a reference standard. There was one exception-the DRESS study showed a somewhat lower correlation for the change score at 18 months (0.787). The loss in power of SENS over SHS was limited to at most 19% (BeSt year 5). In addition, the difference in power between SENS and SHS is smaller at higher levels of power. Conclusion SENS appears to be a reasonable alternative to SHS, with only a limited loss of power to show between-group differences in radiographic progression.

Abstract Background In the randomized controlled LADI trial, a subset of patients with Crohn’s disease (CD) maintained clinical remission following extension of the adalimumab dose interval (1). The aim of this study was to assess long-term clinical outcomes for trial participants who extended the adalimumab interval to 3 or 4 weeks compared to conventional dosing. Methods At baseline, we enrolled CD patients in biochemical and corticosteroid-free clinical remission (CFCR) on adalimumab 40 mg/2 weeks. The intervention group started on a 3-week interval and increased to 4 weeks at week 24, if in clinical and biochemical remission. Controls remained on adalimumab 40 mg/2 weeks. Data >48 weeks was collected between 2017 and 2023. The primary endpoint of the current study was the proportion of patients in CFCR (HBI ≤4 or remission per physician global assessment) at year 3 while maintaining the assigned baseline adalimumab interval (intervention: 40 mg/3-4 weeks, control: 40 mg/2 weeks). Secondary endpoints included biochemical remission (CRP ≤10 mg/L and/or FC ≤250 µg/g), proportion of patients who discontinued adalimumab for stable remission, and adverse events (AEs). Patients without sufficient long-term data were excluded. Results Data was extracted for 143/174 initially randomized subjects (intervention: 95; control: 48). Figure 1 is a Sankey diagram for visualization of patient flow during follow-up. In the intervention group, 30/95 (31.6%) patients maintained de-escalation at 3 years (7 on a 3-week interval, 23 on a 4-week interval) while 4 patients stopped for stable remission. The primary endpoint of CFCR was achieved in 28/95 (29.5%) at year 3, and 23/95 (24.2%) were in biochemical remission. Twenty-eight patients re-escalated to 40 mg/2 weeks, 24/28 were in CFCR at year 3. In the control group, 30/48 (62.5%) patients maintained the 2-week interval after 3 years with 27/48 (56.3%) in CFCR, and 20/48 (41.7%) in biochemical remission. In addition to 4 subjects in each group that stopped adalimumab for stable remission, another 19 patients (13.3%) discontinued adalimumab by year 3 (intervention: n=17/95 (17.9%); control: n=2/48 (4.2%)). Discontinuation reasons were loss of response (n=9, 50.0% (8 in intervention group)), AEs (n=5, 27.8%), adalimumab antibodies (n=4, 22.2%, 3 in intervention group), and 1 missing. AEs are shown in Table 1. Conclusion Long-term follow-up showed that one-third of patients in the intervention group was in remission after continued de-escalation of adalimumab therapy at year 3, while another 25% recaptured remission after dose re-escalation. In the control group, over half of patients maintained remission on adalimumab every 2 weeks. References 1.van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, Atsma F, Kievit W, et al. Increased versus conventional adalimumab dose interval for patients with Crohn’s disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023;8(4):343-55.

Background Musculoskeletal manifestations occur in half of the patients with inflammatory bowel disease (IBD) and contribute to a reduced quality of life (QoL) and increased work disability. We aimed to evaluate the natural disease course, characteristics, and risk factors of musculoskeletal manifestations in patients with IBD. Methods We performed a prospective longitudinal cohort study in patients with IBD with and without musculoskeletal manifestations with a 1-year follow-up. Primary outcome was the proportion of patients with resolution of musculoskeletal manifestations. Secondary outcomes included the proportion of patients with IBD that developed new musculoskeletal manifestations during follow-up; the correlation among IBD activity, baseline characteristics, and musculoskeletal disease course; and the difference in QoL between patients with and without musculoskeletal manifestations. Results In total, 243 patients with IBD were included (124 with and 119 without musculoskeletal manifestations). In the majority of patients (62.2%), musculoskeletal manifestations were of noninflammatory nature. Overall, peripheral and axial manifestations were persistent in 85.7 and 44.6% at 1 year, respectively. The QoL at baseline and at 1 year was lower in the group with musculoskeletal manifestations compared with patients without these manifestations. Female sex and age above 40 were associated with the presence of musculoskeletal manifestations. Conclusion Musculoskeletal manifestations in patients with IBD are mostly noninflammatory disorders, persist at 1 year of follow-up, and occur more frequently in patients of age above 40 and female sex. Overall, patients with musculoskeletal manifestations have lower QoL compared with patients without musculoskeletal manifestations.

OBJECTIVES:To compare a bDMARD mode of action cycle vs swap treatment strategy in patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) after first tumour necrosis factor inhibitor (TNFi) discontinuation. METHODS:In December 2019, our local treatment protocol for PsA and axSpA changed from a cycle strategy (first TNFi to second TNFi) to a swap strategy (first TNFi to IL-17i). We performed a retrospective comparison of the 3-year drug retention rate using multivariable Cox regression (ref: cycle group) and disease activity (DAS28-CRP for PsA, BASDAI for axSpA) in patients with a clinical diagnosis of PsA and axSpA. For subgroup analyses, Cox regression models were stratified by sex, reason of first TNFi discontinuation, and (non-)radiographic status in axSpA. RESULTS:In PsA patients (n=406), there was no overall significant difference in drug retention between strategies (HR: 1.17 (95% CI: 0.87 to 1.58), p=0.29), but male PsA patients had a significant higher risk for treatment discontinuation following a swap strategy. In axSpA patients (n=335), the swap strategy was overall associated with a higher risk of treatment discontinuation (HR: 1.46 (95% CI: 1.03 to 2.07), p=0.04). Patients who discontinued their first TNFi due to inefficacy and patients diagnosed with radiographic axSpA were at significant higher risk for treatment discontinuation following a swap strategy. No significant differences in disease activity were found for treatment strategies in PsA or axSpA. CONCLUSION:In PsA, the cycle and swap treatment strategy performed similarly, while in axSpA, the cycle strategy was associated with a significant higher drug retention rate.

BACKGROUND:Scarcity of data on the value of long-term routine laboratory toxicity monitoring (lt-RLTM) during disease-modifying antirheumatic drug (DMARD) use results in frequent monitoring in clinical practice. OBJECTIVE:To determine the cumulative incidence of abnormal and very abnormal laboratory monitoring results among patients with rheumatoid arthritis (RA) and to characterize the clinical context for the incidence of new very abnormal results. DESIGN:Retrospective cohort study. SETTING:The Netherlands, July 2008 to April 2020. PATIENTS:Patients with RA undergoing lt-RLTM after at least 6 months of DMARD use. MEASUREMENTS:Cumulative probabilities of abnormal and very abnormal results were calculated for alanine aminotransferase (>100 and >300 U/L), estimated glomerular filtration rate (eGFR; <60 and <45 mL/min/1.73 m2), hemoglobin (Hb; <7.5 mmol/L [females] or <8 mmol/L [males] and <6 mmol/L), leukocyte count (<3.5 and <2.0 × 109/L), and platelet count (<140 and <100 × 109/L). Chart review for newly occurring very abnormal results was performed for clinical context. RESULTS:4774 patients underwent 59 555 lt-RLTM test sets over 18 383 patient-years. The cumulative probabilities of very abnormal laboratory results for the 5 tests varied from 0.2% (leukocyte count) to 6.6% (eGFR) at 2 years and from 0.3% (leukocyte count) to 11% (eGFR) at 5 years. New very abnormal results (n = 449) mostly occurred after a dose increase (6.5%), were often already known or suspected (47.7%), were considered to be unrelated to DMARD use (24.1%), or did not lead to action (35.8%). The incidence of less serious abnormal results was higher, as high as 39% for eGFR less than 60 mL/min/1.73 m2 and 61% for Hb level below 7.5 mmol/L for females or below 8 mmol/L for males. LIMITATION:The possibility that regular monitoring contributed to lack of serious adverse outcomes cannot be excluded. CONCLUSION:Routine laboratory monitoring after 6 months of DMARD use revealed that most very abnormal laboratory results were already clinically anticipated and often occurred after dose escalation, although the cumulative incidence of some less serious abnormal results was quite high. Strategies for lt-RLTM warrant reconsideration. PRIMARY FUNDING SOURCE:None.

BackgroundIt remains unclear if the increased colorectal neoplasia detection rate in inflammatory bowel disease (IBD) by high-definition (HD) dye-based chromoendoscopy compared with HD white-light endoscopy is due to enhanced contrast or increased inspection times. Longer withdrawal times may yield similar neoplasia detection rates as found by HD chromoendoscopy.ObjectiveTo compare colorectal neoplasia detection rates for HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy, using single-pass HD white-light endoscopy as an additional control group.DesignIn a multicentre, randomised controlled trial, IBD patients aged ≥18 years without active disease and scheduled for endoscopic surveillance were included. Patients were 2:2:1 randomised to HD white-light endoscopy with segmental re-inspection of each colonic segment (double pass), HD chromoendoscopy or single-pass HD white-light endoscopy. The primary outcome was colorectal neoplasia detection rate. Assuming equal colorectal neoplasia rates (non-inferiority margin of 10%) between segmental re-inspection and chromoendoscopy and superiority of segmental re-inspection vs single-pass HD white-light endoscopy, a sample size of 566 patients was required.ResultsIn total, 563 patients were analysed per-protocol. Colorectal neoplasia detection rates were 10.3% (n=24/234) for HD white-light endoscopy with segmental re-inspection and 13.1% (n=28/214) for HD chromoendoscopy. This confirmed non-inferiority to HD chromoendoscopy (Δ−2.8%, lower limit 95% CI −7.8, p<0.01). In addition, the number of detected colorectal neoplasia per 10 min of withdrawal time was similar between HD white-light endoscopy with segmental re-inspection and HD chromoendoscopy (0.062 vs 0.058, p=0.83). Single-pass HD white-light endoscopy yielded a lower colorectal neoplasia rate (6.1%; n=7/115) than segmental re-inspection but this was not statistically significant (Δ4.1%, 95% CI −2.2:9.6%, p=0.19).ConclusionsHD white-light endoscopy with segmental re-inspection was non-inferior to HD chromoendoscopy for colorectal neoplasia detection in IBD patients. It can therefore be assumed that the benefit of HD chromoendoscopy may be explained by the longer withdrawal time and not necessarily the enhanced contrast. However, re-inspection per se did not lead to a significantly higher colorectal neoplasia rate than single-pass HD white-light endoscopy alone.

Objectives Methotrexate is recommended in current guidelines as a first-choice glucocorticoid (GC)-sparing agent for patients with polymyalgia rheumatica (PMR) prone to relapses or prolonged GC use. Previous randomised controlled trials (RCTs) have reported conflicting results but used low doses of methotrexate (7.5-10 mg/wk). More evidence on higher doses (25 mg/wk) is needed. Methods In this 52-week blinded, placebo-controlled RCT, patients with recently diagnosed PMR (per 2012 European League Against Rheumatism/American College of Rheumatology criteria) and <8 weeks of GC use were randomised 1:1 to methotrexate 25 mg/wk or placebo, alongside a 24-week GC-tapering protocol. The primary outcome was GC-free remission (Polymyalgia Rheumatica-Activity Score <10 and no GC use) at week 52, tested with a 1-sided Cochran-Mantel-Haenszel test stratified by sex and inflammatory markers. Results Sixty-four patients were recruited, of whom 58 were included in the final analysis. GC-free remission at 52 weeks was achieved in 80% of patients in the methotrexate group vs 46% in the placebo group (risk difference 34%, 1-sided 95% CI: 14%, 1-sided P = .0042). Conclusions This small but high-quality RCT demonstrated that methotrexate 25 mg/wk significantly increases the likelihood of achieving GC-free remission at 52 weeks in newly diagnosed PMR. These findings show a benefit of early introduction of methotrexate in PMR. Further research is needed to determine the optimal timing of methotrexate initiation.

BACKGROUND:Results of the DRESS-PS trial showed that a tapering strategy with TNF inhibitors is non-inferior to continuation of the same TNF inhibitor dose for up to 12 months in patients with psoriatic arthritis and axial spondyloarthritis. This study aimed to describe the effectiveness of TNF inhibitor tapering for up to 24 months in patients who participated in the DRESS-PS trial. METHODS:This study was a 12-month observational extension of the original 12-month, open-label, non-inferiority DRESS-PS trial conducted at the Sint Maartenskliniek, Nijmegen and Woerden, the Netherlands. Patients aged 16 years and older with psoriatic arthritis or axial spondyloarthritis and stable low disease activity for at least 6 months participated in the original DRESS-PS trial. Patients were randomly assigned to either a treat-to-target tapering strategy (the intervention group), which involved extending the interval between TNF inhibitor doses, resulting in doses of 100%, 66%, 50%, or 0% of the defined daily dose, or to a treat-to-target strategy without tapering (the control group). All patients who participated in the DRESS-PS trial were eligible to participate in this extension study, in which treat-to-target tapering was allowed for all patients, and treatment decisions were made through shared decision making between physicians and patients. The primary outcome was the difference between the original intervention and control groups in the proportion of patients with low disease activity at 24 months; this difference (adjusted for stratification factors at randomisation) was compared, without and with imputation, with the prespecified non-inferiority margin of 20% from the original DRESS-PS trial, and non-inferiority was determined from the adjusted 95% CIs. There was no involvement of people with lived experience of psoriatic arthritis or axial spondyloarthritis in the design, recruitment, conduct, analysis, or reporting of this extension study. The DRESS-PS trial was registered with the Dutch Trial Register, NL6771. FINDINGS:Between Jan 8, 2020, and Oct 10, 2022, 114 of the 122 patients from the DRESS-PS trial participated in this extension study: 79 from the original intervention group (40 with psoriatic arthritis, 39 with axial spondyloarthritis) and 35 from the original control group (18 with psoriatic arthritis, 17 with axial spondyloarthritis). Mean age was 50·0 years (SD 14·5). 70 (61%) patients were men and 44 (39%) were women. The proportion of patients with low disease activity at 24 months was 67% (45 of 67 patients) in the intervention group and 72% (23 of 32 patients) in the control group, with an adjusted difference of 5% (95% CI -15 to 24; p=0·64), which exceeded the prespecified non-inferiority margin. With imputation of missing data, the adjusted difference was 2% (-18 to 16; p=0·85), which fell within the non-inferiority margin. 78 (99%) of 79 patients in the intervention group and 31 (89%) of 35 patients in the control group had at least one adverse event over the full 24-month study period (difference 10% [-1 to 21]; p=0·060). There were no significant differences between groups in adverse events of special interest: infections and injection site reactions. INTERPRETATION:Treat-to-target tapering of TNF inhibitors remains effective and safe for the maintenance of low disease activity for up to 2 years in patients with psoriatic arthritis and axial spondyloarthritis. Future research should explore the challenges to implementation of tapering strategies in routine care in these patients. FUNDING:ReumaNederland.

Background: Patients with axial spondyloarthritis (axSpA) who initiate a biological disease-modifying antirheumatic drugs (bDMARD) often experience loss of effectiveness or side effects. The EULAR treatment guidelines then recommend to start another bDMARD, but without preference for cycling within the same bDMARD class or swapping to another mode of action. In the Sint Maartenskliniek (SMK), the Netherlands, the local drug formulary recommended a cycle strategy (TNFi →TNFi) prior to 2019 and a swap strategy (TNFi →IL-17i) after 2019. This resulted in a quasi-experimental study cohort, that allowed us to compare the cycle versus swap strategy. Objectives: (1) to compare the 3-year drug retention rate and 1-year disease activity of a second TNFi (cycle) versus an IL-17i (swap) strategy and (2) to identify patient and disease characteristics associated with the efficacy of cycling versus swapping, in patients with axSpA who failed a first TNFi. Methods: All patients with a clinical diagnosis of axSpA who were prescribed a second TNFi or IL-17i were included from the Integral Rheumatology Information System (IRIS) of the SMK. Patients were grouped as either a cycler or a swapper. Drug retention was based on treatment failure (event) defined as discontinuation due to inefficacy or side effects. Drug retention was analyzed using Kaplan-Meier curve, log-rank test and multivariable cox regression, adjusted for the potential confounding disease and patient characteristics. The mean difference in disease activity (BASDAI) between baseline, 6 months and 12 months was compared between cyclers and swappers using student's t-test. Results: In total, 335 axSpA patients who have visited the SMK between 2012 and 2023 were included. Of them, 270 were cycler and 65 swapper, with similar baseline patient and disease characteristics (Table 1). Overall, 45.2% and 14.4% of the cyclers and 47.7% and 15.4% of the swappers discontinued their second-line bDMARD therapy respectively due to inefficacy and side-effects. At 12 and 24 months, drug retention rates were 80.7% and 64.4% respectively for cyclers, and 64.6% and 55.4% for swappers. Swappers were more likely to experience treatment failure (HR adjusted for sex and discontinuation reason first TNFi: 1.47 (95% CI: 1.04 – 2.09), p = 0.03) (Figure 1). In women and in patients who experienced inefficacy of their first TNFi, swapping resulted in a significant higher risk of treatment failure (HR for women, adjusted for discontinuation reason first TNFi: 1.60 (95% CI: 1.00 – 2.56), p = 0.05 and HR for those with inefficacy of first TNFi, adjusted for sex: 1.76 (95% CI: 1.17 – 2.64), p < 0.01). At 6 months, the mean BASDAI score was 4.48 (sd: 2.10) for cyclers and 4.06 (sd: 2.36) for swappers and at 12 months, this was 4.29 (sd: 2.12) and 3.87 (sd: 2.31) for cyclers and swappers respectively. There were no significant differences in mean difference in BASDAI between cyclers and swappers at any timepoint. Conclusion: After failure to a first TNFi in patients with axSpA, the drug retention rate was higher in the cycle strategy compared to the swap (IL-17i) strategy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Ilse van Es: None declared, Johanna E. Vriezekolk Received grants from Novartis and Eli Lilly, unrelated to work presented in the current abstract, Nathan den Broeder: None declared, Lisan de Beijer: None declared, A.A. den Broeder Received grants for research and quality of care projects to the institution from Lilly, Abbvie, Galapagos, Novartis, Pfizer, Gilead, Sanofi, Biogen and Celltrion, Noortje van Herwaarden: None declared, E.A.M. Mahler Received grants for research and quality of care projects to the institution from Abbvie, Eli Lilly, Pfizer, Novartis, unrelated to work presented in the current abstract, Emmerik F.A. Leijten Received funding for research grants from Novartis and Eli Lilly, unrelated to work presented in the current abstract.

Objective Current recommendations suggest that patients with newly presenting arthritis suspected of rheumatoid arthritis (RA) should undergo routine radiographs of hands and feet (X‐HF) as the presence of RA‐associated erosions might be of diagnostic and prognostic value. Our objective was to investigate the prevalence, diagnostic, and prognostic value of RA‐associated erosions seen on routine X‐HF in a large, recent cohort of patients with newly presenting arthritis. Methods A retrospective cohort study was performed between 2016 and 2019 in patients with newly presenting arthritis suspected of RA. Patients were included if arthritis was present at diagnosis, rheumatoid factor and anticitrullinated protein antibodies were measured, RA was noted in the differential diagnosis, and routine X‐HF were conducted. Outcomes were the prevalence of one or more RA‐associated erosion(s), and whether diagnostic or prognostic classification were changed by erosivity. Seronegative patients, patients without acute phase reactants, and patients with longer symptom duration were analyzed as subgroups. Results RA‐associated erosions were found in 32 of 724 patients (4.4%, 95% confidence interval [95% CI] 3.1–6.2). Erosions led to a change of diagnostic classification in two patients (0.3%, 95% CI 0.01–1.1) and changed prognostic classification in three patients (0.4%, 95% CI 0.1–1.3). Seronegative patients and patients without elevated acute phase reactants had significantly lower prevalence of erosions ( χ 2 9.4, P = 0.002, χ 2 6.5, P = 0.01). Longer symptom duration was not associated with a different prevalence of erosions ( χ 2 0.4, P = 0.81). Conclusion The recommendation of conducting routine X‐HF in patients with newly presenting arthritis suspected of RA might be reconsidered due to low prevalence of early erosive disease and lack of diagnostic and prognostic value. image

Background The REDO trial (REtreatment with Rituximab in RhEmatoid arthritis: Disease Outcome after Dose Optimisation) showed similar disease activity for retreatment with ultralow doses (200 mg and 500 mg per 6 months) compared with standard low-dose rituximab (RTX, 1000 mg per 6 months). We performed an observational extension study of the REDO trial to assess long-term effectiveness.Methods Patients from the REDO trial were followed from start of the trial to censoring in April 2021. RTX use was at the discretion of patient and rheumatologist using treat to target. The primary outcome was disease activity (disease activity score in 28 joints C-reactive protein (DAS28-CRP)), analysed using a longitudinal mixed model by original randomisation and time-varying RTX dose. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used. RTX dose and persistence, safety and radiological outcomes were also assessed.Findings Data from 126 of 142 REDO patients was collected from 15 December 2016, up to 30 April 2021. Drop-outs continued treatment elsewhere (n=3) or did not consent (n=13).Disease activity did not differ by original randomisation group: 1000 mg mean DAS28-CRP (95% CI) of 2.2 (2.0 to 2.5), 500 mg 2.3 (2.1 to 2.4) and 200 mg 2.4 (2.2 to 2.5). Lower time-varying RTX dose was associated with higher DAS28-CRP (0.22 (95% CI 0.05 to 0.40) higher for 200 mg/6 months compared with 1000 mg/6 months), but remained within the NI-margin. RTX persistence was 93%. Median RTX dose was 978 mg (IQR 684–1413) per year, and no association was found between RTX dose and adverse events or radiological damage.Interpretation Long-term use of ultralow doses of RTX is effective in patients with rheumatoid arthritis responding to standard dose RTX.