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.

Development and validation of a self-administered questionnaire measuring essential knowledge in patients with rheumatoid arthritis.

To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0-100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with < 5% missing data. Internal validity coefficient was 0.90. Mean (standard deviation) long-form score was 72.8 ± 17.8, with lower scores in comorbidity and self-care and higher scores in adaptive skills. Reproducibility was good (0.86 [0.80; 0.92]). RAKE score was positively correlated with the patients' level of education and the HPs' opinion on the patients' knowledge. RAKE score showed good sensitivity to change: 66.8 ± 16.4 then 83.8 ± 12.7, representing a hedges effect size of 1.14 [95% CI 0.73; 1.55]. RAKE is an updated questionnaire assessing essential knowledge for patients with RA to enhance self-management according to current guidelines and the patients' perspective. RAKE can usefully inform patient education interventions, routine care and research.

Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Moderate to Severe Active Rheumatoid Arthritis: TANDEM Study.

INTRODUCTION: Drug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: This non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan-Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5). RESULTS: At inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%-69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age. CONCLUSIONS: This real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient's profile (age, BMI), methotrexate doses, and TCZ-SC use. TRIAL REGISTRATION: NCT02608112.

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.

Low and stable prevalence of rheumatoid arthritis in northern France.

OBJECTIVES: Few data are available on the prevalence of rheumatoid arthritis (RA) in France. Results of the Epidémiologie des rhumatismes inflammatoires (EPIRHUM-2) study suggest a lower prevalence in northern France (0.13%) than nationwide (0.31%) or in southern France (0.66%). Here, our objective was to confirm the lower prevalence of RA in northern France than in the rest of the country or in Europe. METHODS: We used the universal health insurance database to identify patients with RA in northern France (Nord-Pas de Calais region) in 2005. RESULTS: Seven thousand one hundred and twenty-eight patients of the 3,617,224 individuals receiving health insurance under the plan for salaried workers in the Nord-Pas de Calais region (89.3% of the population in the region) were listed as receiving free care for RA, yielding a prevalence of 197.1/100,000 population (female-to-male ratio, 2.99:1; mean age, 60.8 years). DISCUSSION: The prevalence of RA in northern France (0.197% in 2005) is lower than in southern France and northern Europe; thus, the prevalence gradient in France is in the opposite direction to the decreasing north-to-south gradient previously described in Europe. Although environmental and genetic factors involved in the pathogenesis of RA may be involved, the main explanation to the low prevalence in northern France may be the young age of the population.