Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

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.

Colour Doppler ultrasound of temporal arteries for the diagnosis of giant cell arteritis: a multicentre deep learning study.

OBJECTIVES: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. In recent years, colour Doppler ultrasound of the temporal arteries (CDU) has proven to be a powerful non-invasive diagnostic tool, but its place in the diagnosis of GCA remains to be defined. A limitation of the CDU is the inter-operator reproducibility. Image analysis from a different perspective is now possible with the development of artificial intelligence algorithms. We propose to assess this technology for the detection of the halo sign on CDU images. METHODS: Three public hospitals retrospectively collected data from 137 patients suspected of having GCA between January 2017 and April 2019. CDU images (n=1,311) were labelled with the VIA software. Three sets (training, validation and test) were created and analysed with a semantic segmentation technique using a U-Net convolutional neural network. RESULTS: The area under the curve (AUC) was 0.931 and 0.835 on the validation and test set, respectively. An image positivity threshold was determined by focusing on the specificity. With this threshold, a specificity of 95% and a sensitivity of 60% were obtained for the test set. The analysis of the false interpretation showed that the acquisition modalities and the presence of thrombus caused confusion for the algorithm. CONCLUSIONS: We propose an automated image analysis tool for GCA diagnosis. The 2018 EULAR guidelines for image acquisition must be respected before generalising this algorithm. After external validation, this tool could be used as an aid for diagnosis, staff training and student education.

Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study.

OBJECTIVES: To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP). METHODS: We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response. RESULTS: This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs. CONCLUSIONS: This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.

Conventional radiography in juvenile idiopathic arthritis: Joint recommendations from the French societies for rheumatology, radiology and paediatric rheumatology.

BACKGROUND: Juvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant. OBJECTIVE: To provide pragmatic guidelines on CR in each non-systemic JIA subtype. METHODS: A multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee. RESULTS: 74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA. CONCLUSION: These first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA. KEY POINTS: • CR is a valuable imaging technique in selected indications. • CR is routinely recommended for peripheral joints, when damage risk is high. • CR is recommended according to the damage risk, depending on JIA subtype. • CR is not the first-line technique for imaging of the axial skeleton.

Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study).

UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.

Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial.

IMPORTANCE: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. OBJECTIVE: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. DESIGN, SETTING, AND PARTICIPANTS: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. INTERVENTIONS: Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. RESULTS: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). CONCLUSIONS AND RELEVANCE: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000441.

Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis.

AIMS: Infliximab, an anti-tumour necrosis factor-α monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA. METHODS: Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model. RESULTS: The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h(-1) (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l(-) 1, and was decreased by 30% when methotrexate was coadministered. CONCLUSIONS: The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA.

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.

Juvenile idiopathic arthritis patients with positive family history of autoimmune thyroid disease might benefit from serological screening: analysis of the international Pharmachild registry.

BACKGROUND: Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry. METHODS: Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses. RESULTS: The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 - 11.1), female sex (OR = 2.2, 95% CI: 1.3 - 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 - 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 - 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD. CONCLUSIONS: This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening.

Abatacept as Monotherapy and in Combination With Methotrexate in Patients With Juvenile Idiopathic Arthritis: Analysis of 2 Phase III Trials.

OBJECTIVE: To describe the efficacy and safety data of children with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with abatacept (ABA) + methotrexate (MTX) or ABA monotherapy when prior MTX use was either ineffective or not tolerated. METHODS: Posthoc analysis of 2 phase III trials of subcutaneous (SC) and intravenous (IV) ABA over 2 years in patients with pcJIA (aged 2-17 years). Patients were stratified by treatment with ABA + MTX or ABA monotherapy and further by prior biologic use. Efficacy outcomes included JIA-American College of Rheumatology (JIA-ACR) responses, Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP), and safety. Descriptive pharmacokinetic analyses were also performed. RESULTS: Efficacy responses (JIA-ACR and JADAS27-CRP) were similar between patients receiving ABA + MTX (n = 310) or ABA monotherapy (n = 99) and persisted over 2 years. Clinical response rates were similar in biologic-naïve patients and prior biologic users; this was independent of MTX use. Across both studies, ABA + MTX and ABA monotherapy displayed similar safety profiles. Pharmacokinetic results revealed similar minimum steady-state trough ABA concentrations between studies. Further, baseline MTX did not influence ABA clearance and was not a significant predictor of JIA-ACR responses. CONCLUSION: ABA monotherapy (SC and IV) was effective and well tolerated in children with pcJIA when prior MTX use was ineffective or not tolerated. Treatment effects of ABA appear to be independent of MTX coadministration. Consequently, ABA monotherapy can be considered for those with prior biologic therapy if MTX use is inappropriate. (ClinicalTrials.gov: NCT01844518 and NCT00095173).

A tool to identify recent or present rheumatoid arthritis flare from both patient and physician perspectives: the 'FLARE' instrument.

INTRODUCTION: There is a lack of consensus about the definition of flare of rheumatoid arthritis (RA) and a measurement tool. OBJECTIVES: To develop a self-administered tool integrating the perspectives of the patient and the rheumatologist, enabling the detection of present or recent-past RA flare. METHODS: The patient perspective was explored by semistructured individual interviews of patients with RA. Two health psychologists conducted a content analysis to extract items best describing flare from the interviews. The physician's perspective was explored through a Delphi exercise conducted among a panel of 13 rheumatologists. A comprehensive list of items produced in the first round was reduced in a four-round Delphi process to select items cited by at least 75% of the respondents. The identified elements were assembled in domains-each converted into a statement-to constitute the final self-administered Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire. RESULTS: The content of 99 patient interviews was analysed, and 10 domains were identified: joint swelling or pain, night pain, fatigue and different emotional consequences, as well as analgesic intake. The Delphi process for physicians identified eight domains related to objective RA symptoms and drug intake, of which only four were common to domains for patients. Finally, 13 domains were retained in the FLARE questionnaire, formulated as 13 statements with a Likert-scale response modality of six answers ranging from 'absolutely true' to 'completely untrue'. CONCLUSION: Two different methods, for patient and physician perspectives, were used to develop the FLARE self-administered questionnaire, which can identify past or present RA flare.

Phenotype and cytokine profile in a TRAPS Syndrome family with TNFRSF1A p.(Thr79Met): Association with sacro-iliitis.

OBJECTIVE: A comparative retrospective and analytic study was performed in 13 members of a family, affected or not by tumor necrosis factor TNF-α receptor-associated periodic syndrome (TRAPS), including one patient with sacro-illitis. METHODS: Clinical features and TNFRSF1A gene analysis were reported for each family member, symptomatic or asymptomatic. Biological features including CRP/SAA, IgD and ex vivo T lymphocytes and myeloid-derived cytokine profile (IL1-ß, IL-1α, IL-1ra, IL-4, IL-10, IL-17, IFN-γ, TNF-α, IL-6) were characterized for all family members. CRP and IgD only were compared with those of 13 axial SA patients with TNF-blockade indication. RESULTS: Symptomatic TRAPS patients presented p.(Thr79Met) variant and generally complained of abdominal pain. They displayed higher SAA/IgD levels and IL-6/IL-1RA/IL-10 production by PBMC compared to asymptomatic family members. IgD serum level was higher in symptomatic members compared to SA patients. The patient with sacro-iliitis displayed the highest cytokine production and IgD serum levels. CONCLUSION: This study describes clinical heterogeneity in a family examined for TRAPS syndrome and reports the first sacro-iliitis in a patient with pathogenic TNFRSF1A variant. Dysregulated PBMC-derived cytokine and Il-10/IgD dysregulation in the patient with sacro-iliitis raises the issue of sacro-iliitis pathophysiology.

Increased remission with fewer corticosteroids and more biologics in rheumatoid arthritis at 7-year follow-up in real-life conditions.

Remission in rheumatoid arthritis (RA) is an important therapeutic target that is not easy to achieve in real-life conditions. Some prognostic factors have been identified but the literature is variable. The objectives of this study were to evaluate the remission rate and the maintenance of remission in patients with RA over 7 years of follow-up in real-life conditions and to identify prognostic factors of long-term remission. Patients with RA seen at the Poitiers University Hospital were identified and clinical and biological data were collected. Data were analysed after 1 year and 7 years. Twice as many patients were in remission at 7 years than at 1 year of follow-up. 48.6% of patients who were not in remission at 1 year obtained remission at 7 years of follow-up. Patients achieving remission were more often receiving coprescription of csDMARDs and bDMARDs. Patients not in remission at 7 years were given more corticosteroids at higher doses. After 7 years of follow-up, low initial disease activity and use of csDMARDs and bDMARDs appeared to be independent positive predictive factors. Once obtained at one year, remission was maintained for 76% of our patients. As a conclusion, modern management of RA, whatever disease duration, leads to remission rates similar to those of early RA after 7 years of follow-up.

Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis.

Objectives: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are different phenotypes of psoriatic disease (PsD), whose underlying specific mechanisms remain incompletely understood. As cytokines are key elements to induce and tune up immune responses to drive inflammatory diseases, our objective was to assess whether clinical features, disease phenotype and PsA and PsO activity were associated with a particular ex vivo cytokine production profile. Methods: Forty-eight patients (37 PsA and 11 PsO) and 11 healthy subjects (HS) were studied. Cytokine production by peripheral blood mononuclear cells (PBMC) that were either unstimulated, or stimulated with LPS or anti-CD3/CD28 antibodies, were analysed by multiplex assay in the culture supernatants. Results: Cytokine signature of PsD includes a high level of TNFα in supernatants of LPS-stimulated PBMC, higher levels of IL-6 and lower levels of IFN-γ and IL-17A after CD3-CD28 stimulation, as well as higher spontaneous IL-1RA and TNFα production compared to HS. High body mass index (BMI) was associated with lower levels of IL-1ß, and metabolic syndrome with lower levels of IFN-γ after LPS stimulation. In PsD, dermatological activity was related with higher IL-17A level, while rheumatic activity was linked with lower levels of IFN-γ and TNFα. Comparing each PsD subtype to HS, IL-1ß and IL-6 productions are higher when using LPS stimulation in PsO patients with higher levels of IL-1ß and IL-1α in peripheral PsA patients after CD3/CD28 stimulation. LPS stimulation induced high levels of IL-17A in peripheral PsA compared to axial PsA. PsA patients with axial PsA share some features with PsO but shows a distinct cytokine pattern compared to peripheral PsA. Conclusion: PsO and the different PsA subtypes exhibit distinct ex vivo cytokine production profiles and common features of the so-called PsD. Analysis of IL-1 cytokine family and IL-6 seems to be of particular interest to distinguish PsO and peripheral PsA since it depends on monocytes in PsO and T-lymphocytes in peripheral PsA. Peripheral cytokine profiles are influenced by rheumatic and dermatological activity of the disease, and also by metabolic syndrome features. Our results highlight the crucial role of immune cell interactions with different patterns of interaction depending on clinical phenotype.

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.

Efficacy in current practice of switching between anti-tumour necrosis factor- α agents in spondyloarthropathies.

OBJECTIVE: Anti-TNF-α agents are remarkably effective in the treatment of SpAs. However, 30% of patients withdraw from anti-TNF-α agents yearly because of inadequate efficacy or side effects. The objective of this study was to assess in current practice the response to a second and a third anti-TNF-α. METHODS: Retrospectively, all records of patients who had received at least two anti-TNF-α agents have been studied. For axial forms, treatment was considered effective if 3 months after switching the patient had a favourable expert opinion or showed an improvement in BASDAI of at least 2 on a scale of 0-10 or an improvement of 50% (BASDAI 50). For peripheral forms, the treatment was considered effective if the patient had a favourable expert opinion or if a clinical improvement of >30% of the swollen and tender joint counts was established. The reasons for switching were: (i) primary non-responder; (ii) loss of efficacy; and (iii) occurrence of side effects. To identify response predictor factors bivariate analysis was performed. RESULTS: Three hundred and seventy-seven patients under anti-TNF-α agents were treated and 99 patients had received at least two anti-TNF-α agents. Twenty-eight of these 99 patients had been treated with three anti-TNF-α agents. Following the failure of a first anti-TNF-α, the response to a second agent was satisfactory in 80.8%. Patients who had received a third anti-TNF-α following failure of the first two also showed a satisfactory response in 82.1%. The reason for switching from the first or second agent was not predictive of the response. CONCLUSION: In the event of failure or intolerance to anti-TNF-α in the treatment of SpAs, performing a first or second switch produces a satisfactory therapeutic response.

Features and Outcomes of Microcrystalline Arthritis Treated by Biologics: A Retrospective Study.

OBJECTIVES: The usual treatments for crystal-associated arthritis are sometimes contraindicated; thus, new therapies against interleukin-1beta (IL-1) have been developed. We evaluated the characteristics of patients who received biological treatment for crystal-associated arthritis. PATIENTS AND METHODS: We conducted a multicentric retrospective observational study in six rheumatology units in western France. Patients receiving a biological treatment for crystal-associated arthritis between 1 January 2010 and 31 December 2018 were included. Improvement was defined as at least a 50% decrease in the count of synovitis and C-reactive protein level. RESULTS: Forty-six patients were included: 31 (67.4%) were treated for gouty arthritis, and 15 (32.6%) for calcium pyrophosphate crystal deposition disease (CCPD). The first biotherapy used was anakinra for 14 patients (93.3%) with CCPD and 31 patients (100.0%) with gout. The first biotherapy course was more efficient in treating gout than in treating CCPD, with success in 28 patients (90.3%) and 5 patients (35.7%), respectively (p = 0.001). Six patients (42.9%) with CCPD stopped their first biotherapy course because of side effects. Among the patients with gout, urate-lowering therapy was more frequently used after (100%) than before the first biotherapy course (67.7%) (p = 0.002). CONCLUSION: Anakinra was prescribed for cases of refractory crystal-associated arthritis or cases with contraindications for usual treatments. The efficacy of anakinra in treating CCPD was not obvious. Patients with CCPD had more side effects. The biotherapy was introduced with a long-term objective, while anti-IL-1 therapies are approved for acute crises only.