Marc Scherlinger

Switching from originator infliximab to biosimilar CT-P13 in real-life: the weight of patient acceptance

OBJECTIVE To explore acceptance and retention rate of biosimilar CT-P13 after switching from originator infliximab (OI) in patients with various rheumatic diseases. METHODS Patients with stable rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA) under OI were proposed to switch to CT-P13 at the same regimen. A prospective cohort of infliximab-naïve patients beginning CT-P13 and a retrospective cohort of patients treated with OI were used as controls. The primary outcome was to evaluate the retention rate of CT-P13. Secondary outcomes were the switch acceptance rate, reasons of failure and safety. RESULTS Switch was proposed to 100 patients and accepted by 89 of them (63 AS, 12 PsA and 14 RA). After a median follow-up of 33 weeks, 72% of patients were still treated with CT-P13. This retention rate was significantly lower than the one found in our retrospective and prospective control cohorts: 88% and 90% respectively (P-value=0.0002). Within patients who asked to be reswitched to OI, 13/25 (52%) presented clinical disease activity, one developed serum sickness and 11 (44%) presented no objective activity. A subanalysis excluding these 11 patients abrogated difference in retention rates between the 3 cohorts (P-value=0.453). After reswitching to OI, patients without objective disease activity claimed to recover original efficacy. CONCLUSIONS Retention rate was lower after switching from OI to CT-P13 compared to our control cohorts. However, this difference faded after excluding patients without objective clinical activity, suggesting a reluctance of patients to the switch and a negative perception of the biosimilar.

New Insights on Platelets and Platelet-Derived Microparticles in Systemic Lupus Erythematosus

Purpose of reviewCurrent knowledge on the role of platelets and platelet-derived microparticles (PMPs) on the immune system has been fast-growing. Systemic lupus erythematosus (SLE) is a systemic auto-immune disorder characterized by a loss of tolerance toward nuclear auto-antigens. Although recent studies allowed a better understanding of SLE pathogenesis, there is an urgent need for the development of new treatments and the identification of new biomarkers to assess the disease activity. We describe here the state-of-the-art knowledge linking platelets and PMPs to SLE.Recent findingsPlatelet system activation is a key event in the pathogenesis of SLE. Circulating immune complexes, anti-phospholipid antibodies, and infectious agents such as virus are the main activators of platelets in SLE. Platelet activation can be monitored through different ways such as P-selectin expression, mean platelet volume, or circulating PMP levels, suggesting their potential use as biomarkers. Upon activation, platelets promote type I interferon production, NETosis, dendritic cell activation, and T and B lymphocyte activation, all essential events contributing to the development of SLE. Of interest, platelets also play a fundamental role in SLE organ disease such as the development of cardiovascular, thrombotic, and renal diseases. Finally, we review current knowledge on drugs targeting platelet activation and their potential impact on SLE pathogenesis.SummaryPlatelets play a major role in SLE pathogenesis and organ disease and represent a great potential for novel biomarkers and drug development.

Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets

Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two phenotypically distincts inflammatory systemic diseases. However, SLE and SSc share pathogenic features such as interferon signature, loss of tolerance against self-nuclear antigens and increased tissue damage such as fibrosis. Recently, platelets have emerged as a major actor in immunity including auto-immune diseases. Both SLE and SSc are characterized by strong platelet system activation, which is likely to be both the witness and culprit in their pathogenesis. Platelet activation pathways are multiple and sometimes redundant. They include immune complexes, Toll-like receptors activation, antiphospholipid antibodies and ischemia-reperfusion associated with Raynaud phenomenon. Once activated, platelet promote immune dysregulation by priming interferon production by immune cells, providing CD40L supporting B lymphocyte functions and providing a source of autoantigens. Platelets are actively implicated in SLE and SSc end-organ damage such as cardiovascular and renal disease and in the promotion of tissue fibrosis. Finally, after understanding the main pathogenic implications of platelet activation in both diseases, we discuss potential therapeutics targeting platelets.

Acceptance rate and sociological factors involved in the switch from originator to biosimilar etanercept (SB4)

OBJECTIVE To study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease. METHODS Patients with a well-controlled rheumatic disease consulting in our rheumatology department were offered the switch for SB4. After oral and written information concerning biosimilar, free choice to accept the switch was left to the patients. The main outcome was primary switch acceptance rate defined by switch acceptance during the initial consult. Real switch adherence, socio-cultural factors and beliefs influencing switch acceptance rate were retrieved during a telephonic interview at distance from the consultation. RESULTS Fifty-two patients were eligible for the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p < 0.001). Other patient characteristics were roughly identical except for a statistical trend in the refusal group toward older age (61.4vs 50.7years, p = 0.08) and longer disease duration (26vs 12.1years, p = 0.05). Despite initial acceptance, two patients did not begin SB4 after receiving negative information by their regular pharmacist. Real SB4 switch rate was 85% (44/52) and 86% (38/44) of patients reported a good experience of the switch. CONCLUSIONS Acceptance rate of the switch from originator to biosimilar etanercept is high. Patient information, physician and pharmacist knowledge on biosimilars should be taken into account in order to improve their diffusion.

Response to: ‘Switching from the bio-originators to biosimilar: is it premature to recommend this procedure?’ by Cantini and Benucci

In their correspondence, Cantini and Benucci1 express their concern about the lack of real-life data supporting the switch from originator to biosimilar biological disease-modifying antirheumatic drugs, as recommended in the recently issued consensus-based recommendations.2 They argue that the Danish Nationwide Biologic (DANBIO) registry reporting real-life data showed a lower than expected retention rate after the switch to biosimilar infliximab (bio-IFX) and etanercept.3 4 Concerning bio-IFX, several other real-life studies have been published so far. One Dutch and one French open studies have examined real-life outcomes of the switch from originator to bio-IFX in patients with inflammatory rheumatic diseases.5 6 Both …

Additional response to the correspondence: ‘Switching from the bio-originators to biosimilar: is it premature to recommend this procedure?’ by Cantini and Bennuci

We read with great interest Cantini and Benucci’s response to our letter.1 However, we would like to add some points to the debate. To date and to our knowledge, every single clinical trial investigating efficacy and safety of biosimilars in rheumatology using a double-blinded design has failed to report any clinical difference with the original biologic. The double-blinded controlled trial NOR-SWITCH as well as open-label extension studies such as PLANETRA investigating efficacy and safety of the switch from original to biosimilar infliximab also failed to report any difference.2 3 These studies unequivocally condone the grade 1b recommendation 6 regarding the efficacy and safety of the switch published …

Long-term follow-up after switching from originator infliximab to its biosimilar CT-P13: the weight of nocebo effect

To date, all available data regarding the switch from bio-originator to its biosimilar are reassuring, and the switch has been recommended as a shared patient–physician decision in recent consensus-based recommendations.1 In particular, the Norways infliximab switching study (NOR-SWITCH study), a 52-week randomised double-blind trial, strongly supports the efficacy and safety of the switch from originator infliximab (OI) to its biosimilar CT-P13 in patients with a stable disease.2 However, long-term follow-up data are required to confirm the efficacy and safety of the switch. In a previous real-life study, we demonstrated a high acceptance of 89% (89/100) and a 72% (64/89) retention rate after a median follow-up of 33 weeks in a cohort of patients with stable rheumatic diseases switched from OI to CT-P13.3 This retention rate was lower compared with two control cohorts: a historic cohort of 82 patients treated with OI in 2013, and …

Monitoring of Epstein–Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) load in patients receiving tocilizumab for rheumatoid arthritis

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 10 mai 2017

A unilateral erosive arthritis in a patient with systemic lupus erythematosus.

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 6 juin 2016