Trial reportClinical pharmacokinetics2020
Population Pharmacokinetic-Pharmacodynamic Relationships of Sarilumab Using Disease Activity Score 28-Joint C-Reactive Protein and Absolute Neutrophil Counts in Patients with Rheumatoid Arthritis.
Trial report in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Ascending Parallel-group Study of the Safety and Tolerability of REGN88 in Subjects With Rheumatoid Arthritis Receiving Concomitant Methotrexate
A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy
A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists
A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists
Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Modeling, Simulation, and Extrapolation to Optimize Pediatric Development Plan: Sarilumab Polyarticular-Course juvenile arthritis Application.Journal of pharmacokinetics and pharmacodynamics · 2026Trial
- Review
- Comprehensive Parent-Metabolite PBPK/PD Modeling Insights Into Methotrexate Personalized Dosing Strategies in Patients With Rheumatoid Arthritis.CPT: pharmacometrics & systems pharmacology · 2025Article
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- A comprehensive review ofFrontiers in pharmacology · 2023Review
- Drug dosing in hospitalized obese patients with COVID-19.Critical care (London, England) · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSarilumab is a human monoclonal antibody blocking the interleukin-6 receptor alpha (IL-6Rɑ) approved for the treatment of moderately to severely active rheumatoid arthritis in adults with inadequate response or intolerance to other disease-modifying antirheumatic drugs.
objectiveThe aim of the current analysis was to describe sarilumab exposure-response relationships.
methodsPopulation pharmacokinetic/pharmacodynamic (PopPK/PD) models were developed describing the time course of the 28-joint disease activity score by C-reactive protein (DAS28-CRP) and absolute neutrophil count (ANC) using data from phase I-III studies (NCT01011959, NCT01061736, NCT01709578, NCT01768572) after subcutaneous sarilumab 50-150 mg every week or 100-200 mg every 2 weeks.
resultsThe time course of DAS28-CRP and ANC after sarilumab administration was described by semi-mechanistic, indirect-response models. Drug effect was predicted to be numerically greater at median exposure for the 200 mg every 2 weeks regimen versus the 150 mg every 2 weeks regimen, for both DAS28-CRP (50% vs. 47%) and ANC reduction from baseline (39% vs. 31%), with the latter showing less fluctuations within a dosing interval. Four covariates were retained in the final models: body weight, baseline rheumatoid factor status, anti-cyclic citrullinated peptide status, and concomitant methotrexate. There was no clinically meaningful influence of investigated covariates for either model.
conclusionThe PopPK/PD models showed numerically greater reductions in DAS28-CRP and ANC with sarilumab 200 mg every 2 weeks than with 150 mg every 2 weeks. There was no clinically meaningful influence of investigated covariates. These data contribute to the totality of evidence that supports a sarilumab subcutaneous starting dose of 200 mg every 2 weeks, with a subsequent reduction to 150 mg every 2 weeks in the event of laboratory abnormalities such as neutropenia.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.