EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.

OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.

Impact of a pharmacist-led programme on biologics knowledge and adherence in patients with spondyloarthritis.

OBJECTIVES: In spondyloarthritis (SpA), improving patients' knowledge on their biologics is a key factor to enhance adherence. The information given to the patient has to ensure the acquisition of safety skills regarding their treatment. The aims of this trial were to evaluate the impact of a pharmacist's educational interview on knowledge and adherence to biologics in these patients. METHODS: Consecutive adult patients with well-controlled axial SpA, stable on biologics were enrolled in a randomised, controlled, single-centre, open-label, 6-month trial. A pharmacist's educational interview provided information on biologics management at baseline in the intervention group and at month 6 in the control group. The changes in a weighted knowledge score concerning the management of biologics and the change in the Medication Possession Ratio (MPR) at month-6 were primary outcomes. The changes in disease activity (BASDAI) and patients' satisfaction regarding the pharmacists' interview were secondary outcomes. RESULTS: Patients' characteristics at baseline were comparable among the 89 included patients (46 in the intervention group, 43 in the control group). The patient's knowledge score concerning biologics management improved at a greater magnitude in the educational group (+11.0±11.5 vs. +3.0 ±10.6 in the intervention versus the control group, respectively, p<0.0001). There was also a trend in a better adherence (+2.2±13.9 vs. -0.6±18.9 in the intervention versus the control group, respectively, p=0.691). The disease activity remained stable in both groups. CONCLUSIONS: This study is strongly in favour of the benefit of a pharmacist's educational interview in the management of patients with axial SpA.

Doctor's aptitude for switching from innovator etanercept to biosimilar etanercept in inflammatory rheumatic diseases: experience from a single French rheumatology tertiary care center.

OBJECTIVES: To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting METHODS: We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. RESULTS: Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p < 0.001). After a 6-month follow-up, bETN retention rate was 83% (95% CI: 0.76-0.92). The first cause of bETN discontinuation was inefficacy (50%). On multivariate analysis, no factor was independently associated with a bETN switch or discontinuation. Drug trough levels did not significantly differ by discontinuation or continuation of bETN. No patient showed anti-drug antibodies. CONCLUSION: The probability of switching from iETN to bETN was likely related to physician characteristics.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice.

OBJECTIVE: To study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. METHODS: A prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). RESULTS: 168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. CONCLUSION: Within the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Impact of a clinical pharmacist in a multidisciplinary consultation on the switch to a biosimilar for inflammatory rheumatic diseases.

OBJECTIVE: Despite several studies proving the efficacy and safety of biosimilars compared with original drugs, switching to a biosimilar remains challenging when the decision is at the discretion of physicians with mandatory consent from patients. Educating patients about biosimilars seems important to increase the prescription rate of biosimilars. This study aimed to evaluate the impact of a clinical pharmacist consultation on the switch to and retention rate of a biosimilar for patients with inflammatory rheumatic diseases. METHODS: This retrospective study compared 2 groups of adult patients receiving (intervention) or not (control) a consultation with a pharmacist right before the rheumatologist consultation. The primary outcome was the frequency of patients who switched to a biosimilar at the end of the rheumatologist visit. RESULTS: We analysed 141 patients (50% women, 50±15years old, on original adalimumab (62%) or etanercept (38%)) who had never used biosimilars: 85 in the intervention group and 56 in the control group. The switch rate to a biosimilar significantly differed between the groups: 69.4% versus 41.1% in the intervention group versus the control group respectively (P<0.01). After a 1-year follow-up period, 72.5% versus 81.3% of patients who switched were still on biosimilar in the intervention versus control group respectively. CONCLUSIONS: This study highlights the positive impact of a pharmacist consultation before the physician's one on switching to a biosimilar, but more studies are needed to assess the impact of this pharmacist consultation on preventing the nocebo effect and therefore on improving the retention rate of biosimilars.

Ultrasound biomicroscopy and optical coherence tomography imaging of filtering blebs after deep sclerectomy with new collagen implant.

PURPOSE: To identify the clinical and anatomic characteristics of filtering blebs after glaucoma surgery with a new biodegradable collagen implant, Ologen, using ultrasound biomicroscopy (UBM) and Visante anterior segment optical coherence tomography (OCT). METHODS: The authors conducted a prospective interventional case series in 15 eyes with openangleglaucoma. The authors performed limbal-based deep sclerectomy with Ologen implantation in the scleral bed. UBM, Visante anterior segment OCT, and a complete ophthalmic examination were performed at each follow-up visit, at 1 day, and 1, 4, and 12 weeks postoperatively. RESULTS: Intraocular pressure (IOP) was significantly reduced (p<0.001) from a mean preoperative value of 24.2-/+6.8 mmHg (n=2.82 glaucoma medications) to a mean postoperative value of 8.1-/+1.2 (n=0), 8.5-/+1.3 (n=0), 11.7-/+3.2 (n=0), and 14.2-/+3.9 mmHg (n=0.33) at 1 day, and 1, 4, and 12 weeks, respectively. Lower IOP correlated with bleb height and low trabeculocorneal membrane thickness (r=0.79, p<0.01, r=0.91, p<0.001) based on UBM examination. Lower IOP correlated with thin bleb wall, large subconjunctival fluid spaces, and low bleb tissue reflectivity (r=0.81, p<0.01, p<0.001, and p<0.001) based on OCT examination. No postoperative complications were reported. CONCLUSIONS: UBM and OCT examinations are useful methods to evaluate outflow mechanisms after glaucoma surgery. Deep sclerectomy with Ologen implantation seems to be an effective and well-tolerated method to reduce IOP.

Reorganising health and social care in Québec: a journey towards integrating care through mergers.

CONTEXT: Two reforms (2014, 2015) characterised by the merger of public health care establishments profoundly shaped the current organisation of Quebec's healthcare system. In 2015, 22 megastructures called Integrated Health and Social Services Centres/Integrated University Health and Social Services Centres (IHSSC/IUHSSC), were created and mandated to organise care delivery to their local populations. OBJECTIVE: To describe the service configuration of the 2015 healthcare system reforms, emphasising on how it shaped the organisation of primary health care (PHC) in Quebec. RESULTS: With the creation of IHSSCs/IUHSSCs, Quebec's healthcare system passed from three to two levels of governance, leading to a centralisation of decision-making powers. Most health services are delivered by the new organisations, while most PHC is delivered by semi-private medical practices, mainly Family Medicine Groups (FMGs). The FMG model is the preferred strategy to develop interdisciplinary team-work and inter-organizational collaborations with other PHC services. CONCLUSION: mechanisms through which centralised healthcare systems achieve community oriented integrated care (COIC) need to be properly understood in order to improve meaningful clinical outcomes. Mergers may not sufficiently achieve integration of services in all its dimensions. These reforms should be monitored and evaluated on their capacity to mobilise all providers as well as physicians to participate in COIC.