Real-world Effectiveness of Sarilumab in RA: Results from the Open-label, Prospective, Single-arm Observational PROFILE Study.

Introduction: The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods: Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set.

The effects of sarilumab as monotherapy and in combination with non-methotrexate disease-modifying anti-rheumatic drugs on unacceptable pain in patients with rheumatoid arthritis: A post-hoc analysis of the HARUKA phase 3 study.

Objectives: To investigate unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and uncontrolled inflammation [C-reactive protein (CRP) ≥1.0 mg/dL] in patients with active rheumatoid arthritis (RA) receiving sarilumab (SAR) as monotherapy or in combination with non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (SAR + csDMARDs).

Methods: In the HARUKA Phase 3 study (NCT02373202), Japanese patients received either SAR monotherapy (n = 61) or SAR + csDMARDs (n = 30).

Efficacy and safety of sarilumab in patients with rheumatoid arthritis stratified by age (<65 and ≥65 years): A post hoc analysis of Japanese Phase 3 clinical trials.

Objectives: This study aimed to assess the efficacy and safety of sarilumab in older patients with active rheumatoid arthritis (RA).

Methods: This is a post hoc analysis of KAKEHASI (NCT02293902) and HARUKA (NCT02373202) trials with stratification by age (<65 and ≥65 years). Patients with moderately to severely active RA were treated with sarilumab in combination with methotrexate or with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy.

Safety of sarilumab in a Japanese population with rheumatoid arthritis by age group: Data from an interim analysis of a postmarketing surveillance study.

Objectives: Using data from a postmarketing surveillance, this interim subgroup analysis investigated the safety of sarilumab in younger (<65 years) and older patients (≥65 and ≥75 years) with rheumatoid arthritis.

Methods: During this interim analysis, patients who were treated with sarilumab in Japan were enrolled between June 2018 and 2021. Data collected by 12 January 2022 were analysed, with adverse drug events monitored over 52 weeks.

Effect of sarilumab on unacceptable pain and inflammation control in Japanese patients with moderately-to-severely active rheumatoid arthritis: Post hoc analysis of a Phase III study (KAKEHASI).

Objective: The aim of this study is to investigate the effects of sarilumab on unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and inflammation in patients with moderately-to-severely active rheumatoid arthritis.

Methods: In this post hoc analysis of the KAKEHASI study, 243 patients received methotrexate with sarilumab 150 or 200 mg or placebo every other week, over 52 weeks. The proportion of patients with UP and correlations of changes in pain VAS from baseline with uncontrolled inflammation (C-reactive protein ≥1 mg/dl) and disease activity indices were assessed.

Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry.

Introduction: Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]).

Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis.

Objective: To evaluate the long-term safety and efficacy of sarilumab with/without conventional synthetic (cs)DMARDs in RA.

Methods: The analyses evaluated two open-label extensions (OLEs): EXTEND and MONARCH OLE, which included patients from six randomized trials. Patients received sarilumab 200 mg once every 2 weeks (q2w) for at least 264 weeks up to 516 weeks (EXTEND: Sarilumab Monotherapy and Sarilumab + csDMARD groups) or for 276 weeks (MONARCH OLE: Continuation and Switch groups).

Clinical Efficacy of Sarilumab Versus Upadacitinib Over 12 weeks: An Indirect Treatment Comparison.

Introduction: The efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs.

Methods: Patient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847).

Haemoglobin changes and disease activity in Japanese patients with rheumatoid arthritis treated with sarilumab.

Objectives: Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis (RA); haemoglobin level changes are associated with changes in disease activity. This post-hoc analysis assessed potential relationships between haemoglobin and disease activity in Japanese patients with RA, enrolled in the KAKEHASI study (NCT02293902).

Methods: In this study, adult patients with moderate-to-severe active RA, who had an inadequate response to methotrexate, were randomised to subcutaneous sarilumab 150 mg every 2 weeks (q2w) or 200 mg q2w or placebo for 24 weeks.

Immunogenicity of sarilumab and impact on safety and efficacy in Japanese patients with rheumatoid arthritis: analysis of two Phase 3 randomised clinical trials.

Objectives: To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA).

Methods: Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA).

Sarilumab monotherapy vs sarilumab and methotrexate combination therapy in patients with rheumatoid arthritis.

Objective: Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24.

Methods: The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue.

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021.

Subcutaneous Sarilumab in Patients With Rheumatoid Arthritis who Previously Received Subcutaneous Sarilumab or Intravenous Tocilizumab: An Open-Label Extension of a Randomized Clinical Trial.

Objective: This post hoc analysis evaluated the safety and efficacy of open-label sarilumab in patients with rheumatoid arthritis (RA) who completed the phase III double-blind ASCERTAIN study (NCT01768572) and switched from intravenous (IV) tocilizumab to subcutaneous (SC) sarilumab, or who continued SC sarilumab in the open-label extension (OLE) study EXTEND (NCT01146652).

Methods: Patients who completed ASCERTAIN were eligible to enroll in EXTEND to receive sarilumab 200 mg SC every 2 weeks (Q2W). Safety and efficacy were reported through 96 weeks in the OLE in patients who switched from tocilizumab IV to sarilumab 200 mg SC Q2W, who switched from sarilumab 150 mg SC Q2W to sarilumab 200 mg SC Q2W, or who continued sarilumab 200 mg SC Q2W.

Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single-Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate.

We assessed pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD relationships of interleukin-6 (IL-6), soluble IL-6 receptor, and C-reactive protein (CRP) in serum, and absolute neutrophil count (ANC) in blood following single doses of subcutaneous sarilumab versus intravenous tocilizumab (NCT02097524) from patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) and on a stable dose of MTX. Patients with RA randomized (1:1:1:1) to single-dose sarilumab (150 or 200 mg subcutaneously) or tocilizumab (4 or 8 mg/kg intravenously) were included (n = 101), and PK, PD, and PK/PD relationships and safety were assessed over 6 weeks postdose. PK profiles for both drugs are described by parallel linear and nonlinear target-mediated clearance pathways.

Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies.

Background: The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups.

Methods: Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs.

Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes.

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs.

Long-term safety and efficacy of sarilumab plus methotrexate on disease activity, physical function and radiographic progression: 5 years of sarilumab plus methotrexate treatment.

Objective: In MOBILITY (NCT01061736), sarilumab significantly reduced disease activity, improved physical function and inhibited radiographic progression at week 52 versus placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate. We report 5-year safety, efficacy and radiographic outcomes of sarilumab from NCT01061736 and the open-label extension (EXTEND; NCT01146652), in which patients received sarilumab 200 mg every 2 weeks (q2w) + methotrexate.

Methods: Patients (n=1197) with moderately to severely active RA were initially randomised to placebo, sarilumab 150 mg or sarilumab 200 mg subcutaneously q2w plus weekly methotrexate for 52 weeks.

Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: A Japan phase 3 trial (HARUKA).

To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA). In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety.

Immunogenicity of Sarilumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant to Disease-Modifying Antirheumatic Drugs.

Introduction: This open-label study evaluated the immunogenicity, safety, and efficacy of sarilumab monotherapy in patients with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response or intolerance to prior conventional synthetic disease-modifying antirheumatic drugs.

Methods: Adults with RA (n = 132) were randomized to receive subcutaneous sarilumab (150 [n = 65] or 200 mg [n = 67]) every 2 weeks (q2w) for 24 weeks. Endpoints included incidence of antidrug antibodies (ADAs) at week 24, safety, and efficacy.