Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

Vollenhoven, Ronald F. van; Keystone, Edward; Strand, Vibeke; Pacheco‐Tena, César; Vencovský, Jiří; Behrens, Frank; Racewicz, Arthur; Zipp, Daniela; Rharbaoui, Faı̈za; Wolter, Ralf; Knierim, Luise; Schmeidl, R.; Zhou, Xuefei; Aigner, Silke; Dälken, Benjamin; Wartenberg-Demand, Andrea

doi:10.1136/annrheumdis-2017-212478

Cited by 12 publications

(10 citation statements)

References 18 publications

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“…In total, 21 studies evaluating bsDMARDs,52–72 18 studies evaluating boDMARDs73–90 and 21 studies evaluating tsDMARDs91–111 were included (online supplementary table S104). Overall, the incidence of major adverse events was low in all RCTs with mostly no differences between the active treatment and placebo or active comparator.…”

Section: Resultsmentioning

confidence: 99%

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

et al. 2020

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ObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).MethodsAn SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomised controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures.ResultsForty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1–3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6–4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors.ConclusionData obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.

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Section: Resultsmentioning

confidence: 99%

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

et al. 2020

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“…IL-12/23 inhibition (ustekinumab) and IL23i (guselkumab) did not show significant differences from placebo. Molecules targeting IL-17A (secukinumab, CNTO6785),26–28 and CD4 (tregalizumab) showed no or only minor efficacy compared with placebo (and lower efficacy compared with abatacept (ABA) as active comparator) in different patient populations 29. Primary efficacy outcomes are summarised in table 2, baseline characteristics are shown in online supplementary table S2.3 and secondary efficacy outcomes in online supplementary table S3.1.…”

Section: Resultsmentioning

confidence: 99%

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis

et al. 2020

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ObjectivesTo inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).MethodsA systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.Results234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.ConclusionThis SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR’s RA management recommendation.

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“… 166 In a phase IIb, randomized, placebo-controlled trial, the efficacy and safety of tregalizumab were measured in patients with active RA. 167 Although tregalizumab was shown to exert biological effects on CD4 modulation, it was not clinically effective compared with placebo. This was probably because that the expected effect would have been achieved after a longer treatment period due to some special mechanisms of Tregs activation.…”

Section: Adoptive Regulatory T Cells Immunotherapymentioning

confidence: 99%

Cell-based therapies for rheumatoid arthritis: opportunities and challenges

Chen

2022

Therapeutic Advances in Musculoskeletal

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Rheumatoid arthritis (RA) is the most common immune-mediated inflammatory disease characterized by chronic synovitis that hardly resolves spontaneously. The current treatment of RA consists of nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic and targeted synthetic DMARDs. Although the treat-to-target strategy has been intensively applied in the past decade, clinical unmet needs still exist since a substantial proportion of patients are refractory or even develop severe adverse effects to current therapies. In recent years, with the deeper understanding of immunopathogenesis of the disease, cell-based therapies have exhibited effective and promising interventions to RA. Several cell-based therapies, such as mesenchymal stem cells (MSC), adoptive transfer of regulatory T cells (Treg), and chimeric antigen receptor (CAR)-T cell therapy as well as their beneficial effects have been documented and verified so far. In this review, we summarize the current evidence and discuss the prospect as well as challenges for these three types of cellular therapies in RA.

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Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

Abstract: NCT01999192; Results.

Cited by 12 publications

References 18 publications

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis

Cell-based therapies for rheumatoid arthritis: opportunities and challenges

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