Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care.

Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.

Angioinvasive aspergillosis mimicking giant cell arteritis in an 81-year-old man with jaw pain and vision loss.

The present case report focuses on an immunocompromised 81-year-old patient initially diagnosed with Waldenström's disease. The patient experienced a gradual vision loss and jaw pain with high erythrocyte sedimentation rate. We first suspected giant cell arteritis, despite inconclusive assessment, including a negative temporal artery biopsy. We rapidly started a corticosteroid pulse therapy followed by high-dose corticosteroid therapy that was followed even after discharge from the hospital. The patient was readmitted 20 days later with severe left retro-orbital pain and progressive left vision loss. Clinical examination revealed complete left eyelid ptosis and unilateral blindness with fixed mydriasis and no eye movement. MRI showed signs of ischaemic optic neuropathy with lysis of the left ethmoid sinus wall; thus, indicating ischaemic optic neuropathy related to lymphoplasmacytic infiltration of Waldenström's disease (Bing-Neel syndrome). Oncological treatment of ibrutinib, a tyrosine kinase inhibitor, was then administered. Despite a favourable prognosis, no improvement was seen. An infectious aetiology was finally confirmed. The left sphenoid sinus biopsy highlighted an angioinvasive aspergillosis with rhino-orbital infiltration observed as ischaemic optic neuropathy. Oncologic treatment was discontinued and antifungal therapy with voriconazole was introduced, leading to a favourable radiological development and analgesic control, without ophtalmological improvement.

[Cases of eosinophilia in patients treated with Tocilizumab for rheumatoid arthritis]. / Éosinophilie chez des patients traités par tocilizumab dans le cadre d'une polyarthrite rhumatoïde.

Hypereosinophilia is a haematological complication that can lead to severe organ damage. This article describes 2 patients who presented eosinophilia under treatment with tocilizumab for rheumatoid arthritis. We will describe the evolution of eosinophilia over time, with the monitoring of medication and discuss the potential link with the treatment as well as the importance of this manifestation in the context of the disease.

L'hyperéosinophilie est une complication hématologique susceptible d'engendrer une atteinte d'organe sévère. Cet article décrit deux patients qui ont présenté une éosinophilie sous un traitement de tocilizumab dans le cadre d'une polyarthrite rhumatoïde. Nous décrivons l'évolution de l'éosinophilie au cours du temps, avec le suivi de la médication, et discutons du lien de causalité éventuel avec le traitement ainsi que l'importance de cette manifestation dans le cadre de la maladie.

Does tenosynovitis of the hand detected by B-mode ultrasound predict loss of clinical remission in rheumatoid arthritis? Results from a real-life cohort.

Objective: The role of US-detected tenosynovitis (USTS) in the management of rheumatoid arthritis remains controversial. The aim of this study was to investigate whether tenosynovitis can predict a flare in rheumatoid arthritis patients in remission in a real-life cohort. Methods: Rheumatoid arthritis patients from the Swiss Clinical Quality Management cohort were included in this study if they were in clinical remission, defined by 28-joint disease activity score (DAS28-ESR) <2.6, and had an available B-mode tenosynovitis score. The patients were stratified according to the presence or absence of tenosynovitis (USTS+ vs. USTS-). Cox proportional hazard models were used for time-to-event analysis until the loss of remission, after adjustment for multiple confounders. The impact of baseline US performed early in remission and the advent of flares at different fixed time periods after baseline were investigated in sensitivity analysis. Results: Tenosynovitis was detected in 10% of 402 rheumatoid arthritis patients in remission. At baseline, USTS+ patients in remission had significantly higher DAS28-ESR (mean (SD): USTS- 1.8 (0.5) versus USTS+ 2.0 (0.5); p = 0.0019) and higher additional disease activity parameters, such as physician global assessment, and simplified- and clinical-disease activity index. Joint synovitis detected by B-mode US was associated with tenosynovitis (mean (SD) 7.2 (6.3) in USTS- versus 9.0 (5.4) in USTS+, respectively; p = 0.02). A disease flare was observed in 69% of remission phases, with no differences in the time to loss of remission between USTS+ and USTS- groups. Conclusion: While US-detected tenosynovitis was associated with higher disease activity parameters in rheumatoid arthritis patients in clinical remission, it was not able to predict a flare.

Incidence of COVID-19 in patients treated with infliximab compared with patients treated with rituximab.

OBJECTIVE: To determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors. METHODS: We included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group. RESULTS: 190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher's exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry. CONCLUSION: While the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.

[Undifferentiated connective tissue disease : what is it ?] / La connectivite indifférenciée : qu'est-ce que c'est ?

The term undifferentiated connective tissue disease (UCTD) describe patients presenting with clinical and serological manifestations of systemic autoimmune diseases but not fulfilling the criteria for any defined connective tissue diseases. The challenge is to differentiate patient with a stable UCTD from patients that will evolve to a connective tissue disease with therapeutic and prognostic impact. This article describe UTCD concept, clinical presentation, evolution, and prognostic factors and patients management.

Le concept de connectivite indifférenciée décrit un patient qui présente un ensemble de symptômes, signes cliniques et résultats biologiques évoquant une maladie auto-immune ou une connectivite, mais sans complètement satisfaire aux critères de classification d'une connectivite spécifique. Il est important de différencier les patients dont la forme de la maladie va rester stable de ceux chez qui elle va évoluer vers une connectivite spécifique en raison de l'impact thérapeutique et pronostique. Cet article décrit le concept de connectivite indifférenciée, sa présentation clinique, son évolution et les marqueurs pronostiques ainsi que la prise en charge des patients.

[Sjögren Syndrome : the ENT specialist contributes to the workup]. / Syndrome de Sjögren : contribution de l'ORL au bilan diagnostique.

Sjögren Syndrome is an autoimmune disorder presenting as Sicca syndrome (dry-eye, dry mouth) and most often multiorgan involvement with various clinical manifestations. The diagnostic criteria defined by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) include biologic, histologic parameters and functional measurements. Part of this workup can be performed by the ENT specialist. It encompasses minor salivary gland biopsy, sialometry, Schirmer lacrymal test and major salivary gland ultrasound. These tests and their performances are described. The growing importance of major salivary gland ultrasound as a follow-up and diagnostic tool is also discussed in this article.

Le syndrome de Sjögren est une maladie auto-immune dont la présentation clinique classique est un syndrome sec oculaire et buccal souvent accompagné d'une atteinte multisystémique aux manifestations cliniques variées. Le bilan diagnostique se compose de différents tests cliniques, histologiques et biologiques définis par l'American College of Rheumatology (ACR) et l'European League Against Rheumatism (EULAR). Une partie de ce bilan peut être effectuée par le médecin spécialiste ORL : la biopsie des glandes salivaires mineures, la sialométrie, le test de Schirmer et l'ultrason des glandes salivaires majeures. Ces tests et leurs performances sont décrits au cours de cet article. L'ultrason des glandes salivaires majeures n'est pour l'heure pas pris en compte dans les critères diagnostiques, mais son rôle dans le bilan et le suivi de la maladie de Sjögren gagne en importance et sera également discuté.

Discordances between clinical and ultrasound measurements of disease activity among RA patients followed in real life.

OBJECTIVE: Measurements of disease activity, such as the clinical disease activity score (DAS28) or ultrasound (US) scores, often yield discordant results. This study's objectives were to determine the proportion of disagreements between the two assessment methods in patients with rheumatoid arthritis (RA) and to describe factors associated with discrepancy in assessment. METHODS: All RA patients in the Swiss registry for inflammatory arthritides (SCQM) with at least one concomitant DAS28 and US score, were included. Disease activity was categorized as remission, low-to-moderate, and high, based on previously established cut-offs, for both the DAS28 and the US score. A longitudinal analysis was performed among patients who underwent at least two assessments. RESULTS: Of 2369 assessments included (1091 patients), 1196 (50.4%) were discordant. The US score both over- and under-estimated disease activity compared to the DAS28 score (23.5% and 26.8% respectively). Clinical and demographic factors significantly associated with discordant results were the individual components of the DAS28 score when US was used as the reference and age, disease duration, and the swollen joint count when the DAS28 was used as the reference. The main US-related factor associated with discordance was the presence of US tenosynovitis. In the longitudinal analysis of 1081 patients, the proportion of disagreements remained essentially unchanged. CONCLUSION: Rates of disagreement between clinical and US assessments of disease activity among RA patients are high and remain high during follow-up, even when the US assessors were aware of the clinical examination findings. Both clinical- and ultrasound- related factors were associated with discordances.

Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years.

OBJECTIVES: To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA. METHODS: In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders. RESULTS: After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup. CONCLUSION: Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.

Ultrasound is not associated with the presence of systemic autoimmunity or symptoms in individuals at risk for rheumatoid arthritis.

Objective: To identify whether musculoskeletal ultrasound (MSUS) abnormalities are associated with specific phases of rheumatoid arthritis (RA) development in individuals at risk of RA. Methods: This is a prospective cohort study of individuals at risk of developing RA, namely first-degree relatives of patients with RA (RA-FDRs) without evidence of established rheumatic disease at inclusion. The inflammatory activity on MSUS was assessed according to a validated score (SONAR). Active MSUS was defined as a total B-mode score greater than 8, including at least one joint with significant synovitis (grade 2 or 3) or significant synovial hyperaemia (Doppler score greater than 1). We used logistic regression to analyse associations between MSUS findings and recognised preclinical phases of RA development, adjusting for other demographic and biological characteristics. Results: A total of 273 RA-FDRs were analysed, of whom 23 (8%) were anticitrullinated protein autoantibodies-positive, 58 (21%) had unclassified arthritis and 96 (35%) had an active MSUS, which was only associated with unclassified arthritis (OR: 1.8, 95% CI 1.0 to 3.3). Conclusion: In individuals at risk of RA, active MSUS was associated with the presence of unclassified arthritis, but not with any of the earlier described phases of RA development. These findings do not support an indiscriminate use of ultrasound in a screening strategy for preclinical RA.

Glucocorticoid injections for greater trochanteric pain syndrome: a randomised double-blind placebo-controlled (GLUTEAL) trial.

Small observational studies suggest that local glucocorticoid (GC) injection may be effective in the management of the greater trochanteric pain syndrome (GTPS). The objective was to perform the first randomised double-blind placebo-controlled trial to investigate the efficacy of local GC injection in the management of GTPS. The trial was conducted between November 2011 and May 2015. Inclusion criteria included lateral hip pain (LHP) for greater than 1 month, a LHP score of ≥ 4/10 and typical LHP reproduced by palpation of the greater trochanter. Participants were randomised in a 1:1 ratio to injection with a combination of local anaesthetic and GC (intervention) or injection with normal saline solution (placebo). The primary outcome of interest was the difference in pain intensity at 4 weeks post-injection between the two groups. Patients were followed for 6 months. A total of 46 patients were included. There were no significant differences between the two groups in terms of pain reduction at 1 month (p = 0.23). When including all measures in the first 4 weeks and using multilevel regression, there was a trend towards improvement in pain scores in favour of the intervention group (p = 0.08). There were no significant differences in pain scores between groups at 3 and 6 months. In the management of GTPS, local glucocorticoid injections are of no greater efficacy than injection of normal saline solution. Given the lack of long-term improvement and the potential for cortisone-related side effects, this intervention is of limited benefit.

Can Ultrasound Be Used to Predict Loss of Remission in Patients with RA in a Real-life Setting? A Multicenter Cohort Study.

OBJECTIVE: Several studies have suggested that patients with rheumatoid arthritis (RA) presenting with ultrasound (US) synovitis despite clinical remission have more subsequent flares than those who show both clinical and sonographic remission. The objective of our study was to investigate whether these results could be translated to a real-life setting. METHODS: We compared the time from the first US performed in clinical remission to loss of remission (defined by a DAS28 > 2.6 or the need for stepping up treatment with disease-modifying antirheumatic drugs) within the Swiss Clinical Quality Management cohort of patients with RA, and we adjusted for relevant confounders. Analyses were repeated for different definitions of US-detected synovitis (US+) using greyscale, Doppler, and combined modes based on previously validated scores, and they were adjusted for relevant confounders. RESULTS: There were 318 RA patients with 378 remission phases included. Loss of clinical remission was observed in 60% of remission phases. Residual US synovitis was associated with a shorter duration of clinical remission (median 2-5 mos) and a moderately increased hazard ratio (HR) for loss of remission (HR 1.2-1.5), with the highest HR for the combined US score. The association between US+ and loss of remission was strongest when the US measurement had taken place early in remission (shorter median duration of 6-20 mos) and when followup time was limited to the first 3 or 6 months (most HR between 2-4). CONCLUSION: US-detected synovitis, particularly when US is performed early in clinical remission, has a moderate predictive power for loss of remission in a real-life setting.

The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis.

Transition from genetic risk to the development of systemic autoimmunity associated with rheumatoid arthritis (RA) is considered a key step for the development of RA and often referred to as the immune onset of the disease. The aim of this study is to identify predictors for the presence of anticitrullinated protein antibodies (ACPA) as a marker of systemic autoimmunity associated with RA in a high-risk population, an ongoing cohort of first-degree relatives of patients with RA. We assessed the presence of ACPA in individuals without clinical evidence of RA. We examined characteristics associated with ACPA positivity using general estimation equations to account for multiple observations per individual. A total of 1159 serum samples from 1025 subjects were analyzed, 69 samples (6%) were ACPA-positive, and 227 (20%) positive for rheumatoid factor. Participants had a median age of 45 years (interquartile range (IQR): 33-55) at baseline and 76% were women. Overall, ACPA positivity increased with age (p < 0.001). Among women, ACPA positivity was particularly associated with the age group 45 to 55 years (p = 0.003), but not among men (p = 0.7). In multivariable adjusted analyses, age older than 45, female sex and tobacco smoking were independently associated with ACPA positivity. In our cohort, the presence of ACPA was associated with older age and peaked in women around age 45 to 55 years, the perimenopausal period, suggesting that the development of ACPA may be favored by the decline in ovarian function.

The importance of sonographer experience and machine quality with regards to the role of musculoskeletal ultrasound in routine care of rheumatoid arthritis patients.

OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will probably soon be integrated in standard care of patient with rheumatoid arthritis (RA). However, in daily care, quality of US machines and level of experience of sonographers are varied. We conducted a study to assess reproducibility and feasibility of an US scoring for RA, including US devices of different quality and rheumatologist with various levels of expertise in US as it would be in daily care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a semi-quantitative score using OMERACT criteria for synovitis and erosion in RA. The score was taught to 108 rheumatologists trained in US. One year after the last workshop, 19 rheumatologists participated in the study. Scans were performed on 6 US machines ranging from low to high quality, each with a different patient. Weighted kappa was calculated for each pair of readers. RESULTS: Overall, the agreement was fair to moderate. Quality of device, experience of the sonographers and practice of the score before the study improved substantially the agreement. Agreement assessed on higher quality machine, among sonographers with good experience in US increased to substantial (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS: This study demonstrated feasibility and reproducibility of the Swiss US SONAR score for RA. Our results confirmed importance of the quality of US machine and the training of sonographers for the implementation of US scoring in the routine daily care of RA.

Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: results of an observational cohort study.

OBJECTIVE: The primary aim of the study was to evaluate whether rheumatoid arthritis (RA) patients considered to be in remission according to clinical criteria sets still had persisting ultrasound (US) synovitis. We further intended to evaluate the capacity of our US score to discriminate between the patients with a clinically active disease versus those in remission. METHODS: This is an observational study nested within the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) rheumatoid arthritis cohort. A validated US score (SONAR score) based on a semi-quantitative B-mode and Doppler (PwD) score as part of the regular clinical workup by rheumatologists in different clinical settings was used. To define clinically relevant synovitis, the same score was applied to 38 healthy controls and the 90st percentile was used as cut-off for 'relevant' synovitis. RESULTS: Three hundred and seven patients had at least one US examination and concomitant clinical information on disease activity. More than a third of patients in both DAS28 and ACR/EULAR remission showed significant gray scale synovitis (P=0.01 and 0.0002, respectively) and PwD activity (P=0.005 and 0.0005, respectively) when compared to controls. The capacity of US to discriminate between the two clinical remission groups and patients with active disease was only moderate. CONCLUSION: This observational study confirms that many patients considered to be in clinical remission according the DAS and the ACR/EULAR definitions still have residual synovitis on US. The prognostic significance of US synovitis and the exact place of US in patients reaching clinical remission need to be further evaluated.

Ultrasound evaluation of synovitis in RA: correlation with clinical disease activity and sensitivity to change in an observational cohort study.

OBJECTIVE: To evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. METHODS: One hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. RESULTS: In the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r = 0.41, P < 0.0001). The same was true for the PwD score (r = 0.41, P < 0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r = 0.54, P < 0.0001 and r = 0.46, P < 0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). CONCLUSIONS: The SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

[The differential diagnosis of tenosynovitis]. / Diagnostic différentiel des ténosynovites.

Etymologically a ténosynovites means inflammation of a tendon sheath. We recognize two separate presentations: exsudative and stenosing. The wide differential diagnosis includes infections, most of chronic inflammatory joint diseases, mainly connective tissue disorders, rheumatoid and psoriatic arthritis, pathology related to mechanical stress as De Quervain's tenosynovitis or trigger finger and unusually tumor. Diabetes is a risk factor for most of them and is related to poor prognosis. Musculoskeletal ultrasound is useful for diagnosis and to guide procedure as fluid aspiration or steroid injection.

B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents.

OBJECTIVE: Patients with rheumatoid arthritis (RA) in whom the response to anti-tumor necrosis factor (anti-TNF) therapy is inadequate have several therapeutic options, such as switching to an alternative anti-TNF agent or initiating B cell-depleting therapy with rituximab (RTX). Although both therapeutic options have been proven effective in trials, no head-to-head comparisons are available. The aim of this study was to compare the effectiveness of RTX with that of an alternative anti-TNF agent in the management of patients with RA who had an inadequate response to anti-TNF therapy. METHODS: This prospective cohort study was nested within the Swiss Clinical Quality Management RA cohort and included all patients who had an inadequate response to at least 1 anti-TNF agent and subsequently received either 1 cycle of RTX or an alternative anti-TNF agent. The primary outcome was the evolution of RA disease activity (as measured on the Disease Activity Score in 28 joints [DAS28]), which was analyzed using multivariate regression models for longitudinal data. RESULTS: One hundred sixteen patients with RA were included; 50 patients received 1 cycle of RTX, and 66 patients were treated with a second or a third alternative anti-TNF agent. At baseline, there were no significant differences between the 2 groups in age, sex, disease duration, and disease activity. Evolution of the DAS28 was more favorable in the group that received RTX compared with the group that received an alternative anti-TNF agent (P = 0.01). At 6 months, the mean decrease in the DAS28 was -1.61 (95% confidence interval [95% CI] -1.97, -1.25) among patients receiving RTX and -0.98 (95% CI -1.33, -0.62) among those receiving subsequent anti-TNF therapy. CONCLUSION: The results of this observational study suggest that treatment with RTX may be more effective than switching to an alternative anti-TNF agent in patients with RA in whom active disease persists despite anti-TNF therapy.