Retention rate of subcutaneous TNF inhibitors in axial spondyloarthritis in a multicentre study from the RIC-FRANCE network.

The objectives of our study were to assess retention rate, safety, and predictive factors for retention of subcutaneous (SC) TNF inhibitors (TNFi) (adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZP)) in axial spondyloarthritis (axSpA) depending on the line of treatment in real-life conditions. A multicentre retrospective observational study was conducted including 552 patients fulfilling the ASAS criteria for axSpA followed in the RIC-France register who began SC-TNFi between 01/01/13 and 08/31/2018 for a total of 824 prescriptions. Taking all lines of treatment into account, GOL had a significantly higher retention rate compared with ADA, ETN, and CZP with a mean retention length of 59 months. As first-line bDMARDs, GOL had a significantly higher retention rate compared with ADA and ETN. ETN had the best retention rate when prescribed as at least 3rd bDMARD. Taking all lines of treatment into account, female sex, peripheral disease, BASDAI at initiation, and line of treatment were predictive factors for treatment cessation. Primary inefficiency was the most frequent reason for treatment cessation. In conclusion, GOL showed the highest retention rate in axSpA. Male sex, absence of peripheral disease, and early line of prescription were associated with better SC-TNFi retention in axSpA.

Differential retention of adalimumab and etanercept biosimilars compared to originator treatments: Results of a retrospective French multicenter study.

Objectives: Previous studies demonstrated equivalence in terms of efficacy and safety of biosimilars (bsDMARDs) compared to original treatments (boDMARDs) and in switching situations. Less is known about what happens when initiating a bsDMARD in a molecule naïve patient. The objectives of our study were to compare the retention of treatment of subcutaneous boDMARDs and bsDMARDs globally, depending on the disease [rheumatoid arthritis (RA), spondyloarthritis (SpA), or psoriatic arthritis (PsA)], molecule [etanercept (ETN) or adalimumab (ADA)], line of treatment, or presence of citrate in the context of first use of each molecule (namely initiation) and to analyze treatment retention's predictive factors. Materials and methods: This multicenter retrospective study used data from shared medical records of the RIC-FRANCE network, encompassing the prescription of hospital rheumatologists and attached practitioners, of patients with RA, SpA, or PsA, with the starting ETN between 03/10/2016 and 31/07/2020, or ADA between 23/10/2018 and 31/07/2020. Clinical data were collected from medical records. Retention analysis was performed using Kaplan-Meier curves and the log-rank test. Retention's predictive factors were analyzed using Cox proportional-hazard ratio. Results: Eight hundred forty-five prescriptions were analyzed: 340 boDMARDs and 505 bsDMARDs. About 57% of prescriptions concerned women. The mean age was 51.8 years. About 38% were prescriptions for RA, 16% for PsA, and 46% for SpA. An increase in the initiation over time was observed for both ETN and ADA. The retention rate of bsDMARDs was superior to boDMARDs' one (39 vs. 23 months; p = 0.045). When molecules are compared, the difference was significant only for ETN (45 vs. 19 months for boDMARD; p = 0.0265). When comparing diseases, the difference in favor of bsDMARDs was significant in patients with RA only (p = 0.041). Citrated treatments displayed better retention compared to citrate-free treatments (p = 0.0137). Multivariable analysis of predictive factors for the cessation of treatment found shorter disease duration, boDMARD prescription, hospital practitioner prescription, late line of treatment, and female sex as significant. More side effects were observed with boDMARDs, especially more infections (17.8% vs. 7.8%). Conclusion: Even if bsDMARDs' prescription increases over time, its penetration rate is still below expectations. bsDMARDs displayed better retention compared to boDMARDs, especially for ETN, and in patients with RA. Citrated treatments had better retention. Prescription by a full-time hospital-based rheumatologist is associated with poorer retention.

Lymphoma complicating rheumatoid arthritis: results from a French case-control study.

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.

Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison.

OBJECTIVES: To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. METHODS: In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. RESULTS: A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. CONCLUSION: In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Actual Persistence of Abatacept in Rheumatoid Arthritis: Results of the French-Ric Network.

OBJECTIVES: Data on abatacept (ABA) persistence in routine practice are limited. We aimed to study ABA persistence rates at 12 months, according to the date of initiation, and to analyze the factors associated with persistence at 12 months. METHODS: We performed an observational, ambispective, multi-center study from January 2008 to July 2016, based on the French-RIC Network. We defined three groups of patients followed up for rheumatoid arthritis (RA), according to the date of initiation of ABA therapy: Group 1 (from 2007 to 31 July 2010: ABA indicated after anti-TNF failure); Group 2 (from 1 August 2010 to 31 March 2014: ABA indicated after conventional antirheumatic drugs failure); Group 3 (from 1 April 2014 to 1 July 2016: ABA available by the subcutaneous injection). RESULTS: Among 517 patients who initiated ABA, drug persistence at 12 months was 68%. The only factor significantly associated with persistence rate at 12 months was C-reactive protein (CRP) < 10 mg/L at ABA initiation (odds ratio (OR) 0.6, 95% confidence interval 0.3-0.9; p = 0.0016). There was no significant difference in drug persistence according to date of initiation, the line of biological disease-modifying antirheumatic drugs (bDMARD) therapy or the route of administration. CONCLUSIONS: In routine practice, over time, ABA has come to be initiated earlier in the course of therapy for RA in France. Abatacept persistence is similar to that reported in the Orencia Rheumatoid Arthritis (ORA) registry, and does not differ according to the date of initiation. The only factor found to be associated with the persistence rate at 12 months was CRP < 10 mg/L at ABA initiation.

Tocilizumab Effectiveness After Switching from Intravenous to Subcutaneous Route in Patients with Rheumatoid Arthritis: The RoSwitch Study.

INTRODUCTION: The main objective of this work was to assess the maintenance of effectiveness of subcutaneous tocilizumab 6 months after switching from intravenous to subcutaneous formulation in patients with rheumatoid arthritis (RA) in a real-world setting. Secondary objectives aimed to describe the characteristics of patients and disease, the effectiveness at 12 months after switching, the therapeutic maintenance, and to search for predictive factors of switching. METHODS: We analyzed all the RA patients of the shared medical file "RIC Nord de France", treated with tocilizumab, switching or not from intravenous to subcutaneous tocilizumab, between April 2015 and January 2016. The primary effectiveness endpoint was the proportion of patients remaining in their DAS28-ESR category remission/low disease activity (LDA) or moving to an inferior DAS28-ESR category at 6 months. Since RoSwitch was an observational study, without randomization, a propensity score was built in a sensitivity analysis to balance on RA and patients' characteristics at inclusion between switching and no-switching groups. RESULTS: An improvement of initial DAS28-ESR category or maintenance in DAS28-ESR remission/LDA at 6 months was shown in 203 of the 285 patients with an evaluation for the primary criterion (71.2%, 95% CI [65.6-76.4%]) without differences between groups (73.3%, 95% CI [63.0-82.1%] vs. 70.3%, 95% CI [63.3-76.6%]). The RoSwitch study showed the maintenance of effectiveness at 6 and 12 months. Similar therapeutic maintenance rates were observed for switch and no-switch patients. No clinical factor was associated with the switch in patients in remission/LDA at inclusion. CONCLUSIONS: The RoSwitch study showed the maintenance of effectiveness at 6 months in RA patients switching from intravenous (IV) to subcutaneous (SC) tocilizumab. FUNDING: Roche SAS and Chugai Pharma France.

Factors associated with knowledge and safety skills of arthritis patients receiving biologics: A survey of 677 patients.

OBJECTIVE: We aimed to determine patient and rheumatologist factors associated with the safety skills of patients receiving bDMARDs for inflammatory arthritis. METHODS: Data were obtained from a descriptive observational cross-sectional nationwide survey performed in 2011 in France. Community- and hospital-based rheumatologists were selected at random. The BioSecure questionnaire was used to collect information on patient safety skills. RESULTS: Of the 677 patients included (mean age 53±13years old; 452 (67%) women, 411 (61%) had RA; 421 (64%) received subcutaneous bDMARDs). Patients had received information about their treatments from their physician 610 (90%), a nurse 207 (31%), by a written booklet 398 (59%), and/or during therapeutic patient education (TPE) sessions 99 (15%). The median BioSecure total score was 72/100 (IQR 60-82). In total, 99 (16.4%) patients had a low skill level; 321 (53.2%) a moderate skill level and 183 (30.3%) a high skill level. On multivariate regression analysis, as compared with high safety skills, low skills were associated with living alone (OR 2.8 [95% CI 1.3â¿¿6.0]), low educational level (OR 4.3 [2.1â¿¿8.9]), living in a large city (OR 3.1 [1.2â¿¿8.2]), being unemployed (OR 3.3 [1.6â¿¿6.7]) and not receiving written information, participating in TPE sessions or consulting a nurse (OR 3.8 [1.6â¿¿8.8]). One rheumatologist-related factor was a high number of patients receiving bDMARDs in the practice. CONCLUSION: We reveal factors associated with low safety skills of patients receiving bDMARDs for inflammatory arthritis, which should be addressed to improve safety skills in this population.

Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated with immunosuppressants: a French retrospective multicenter study.

The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2-20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3-55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure.

Cross-sectional study of self-care safety skills in 677 patients on biodrugs for inflammatory joint disease.

RATIONALE: Biodrugs carry specific risks that patients must be aware of and capable of managing. Until now, few studies have addressed the self-care safety skills of patients taking biodrugs. The primary objective of this study was to describe the self-care safety skills of patients taking biodrugs for chronic inflammatory joint disease. METHODS: We conducted a nationwide cross-sectional survey. To obtain the most representative sample possible of patients taking biodrugs, we selected rheumatologists at random from the directory of the French Society for Rheumatology (SFR). Each rheumatologist was to include 5 consecutive patients receiving biodrugs. The BioSecure questionnaire was used to collect information on patient self-care safety skills. RESULTS: Of the 677 included patients, with a mean age of 53 years, 33% were males, 62% had rheumatoid arthritis, and 47% had previously received a therapeutic patient education (TPE) session. The median BioSecure score (percentage of correctly answered items) was 73% (interquartile range, 60-82). The dimensions with the lowest scores were the symptoms requiring a physician visit (median, 75), vaccinations (median, 75), contraception (median, 50), and subcutaneous biodrugs (median, 68). The replies to theoretical items (assessing knowledge) and those to problem-case items (assessing adaptive skills) were discordant. CONCLUSION: This study provides concrete data of use for improving the information and TPE of patients taking biodrugs. Skills regarding the symptoms that require a physician visit, vaccinations, contraception, and subcutaneous treatments need to be improved. Interesting information can be obtained by simultaneously testing knowledge and coping.

Safety of biologics: elaboration and validation of a questionnaire assessing patients' self-care safety skills: the BioSecure questionnaire. An initiative of the French Rheumatology Society Therapeutic Education section.

BACKGROUND: Biologics are known to entail specific risks (e.g. infections). Patients should possess self-care safety skills to develop appropriate behaviors in situations of risks (e.g. fever). To date, there is no adequate tool to assess these skills. OBJECTIVES: To elaborate a questionnaire to measure knowledge and skills regarding safety issues, for patients treated by biologics. METHODS: Three-step process. (1) A steering group of 10 rheumatologists, one pharmacist and two allied health professionals elaborated an exhaustive list of safety skills. Through a 3-round Delphi process involving the steering group, 14 patients on biologics and 14 other allied health professionals, the list of skills was reduced. (2) A corresponding series of questions and of clinical situations with multiple-choice answers were designed. (3) Preliminary validation was performed against the physician's opinion on skills, and reliability was assessed. RESULTS: The list includes 24 skills e.g. how to deal with fever, planned surgery, dental care, travel, minor traumas, and immunizations. A 55-question questionnaire was constructed. Preliminary validation (62 patients) showed the questionnaire was filled in 10 minutes (median) and correlated to the physician's opinion of skills (R=0.47, P<0.0001) but not to disease status or disease duration. The median score was 75% (range 20%-96%). The questionnaire was reliable: intraclass correlation coefficient, 0.83 (95% CI: 0.63-0.93). CONCLUSION: A simple (multiple-choice questionnaire) and valid tool investigating a core set of safety skills has been developed. This tool could be useful to detect further educational needs regarding biologics safety, and to assess the efficacy of oriented educational interventions.

Use of disease-modifying antirheumatic drugs in patients with psoriatic arthritis.

UNLABELLED: Few prospective placebo-controlled studies have evaluated disease-modifying antirheumatic drugs (DMARDs) in the treatment of peripheral psoriatic arthritis. OBJECTIVE: To evaluate second-line treatments used in clinical practice in patients with psoriatic arthritis. METHOD: We studied a cross-section of 100 consecutive patients seen by hospital-based or office-based rheumatologists for psoriatic arthritis. PATIENTS: The 55 men and 45 women had a mean age of 48 years (range, 17-79 years) and a mean disease duration of 7 years (range, 1-24 years). RESULTS: The most commonly used DMARDs were sulfasalazine, gold, methotrexate, and hydroxychloroquine (64, 43, 41 et 17 patients, respectively). These drugs had been stopped because of inefficacy in 31%, 31%, 12%, and 53% of patients, respectively, and because of adverse events in 23%, 44%, 22%, and 41% of patients, respectively. At the time of the study, mean treatment durations were 15, 21, 34, and 12 months, respectively, and the drugs were still being used in 45%, 21%, 66%, and 6% of patients. CONCLUSION: Our data confirm the value of methotrexate and salazopyrine. Methotrexate had the best risk/benefit ratio. Gold was often responsible for side effects. Hydroxychloroquine was inadequately effective and poorly tolerated.