Structural damage progression in patients with early rheumatoid arthritis treated with methotrexate, baricitinib, or baricitinib plus methotrexate based on clinical response in the phase 3 RA-BEGIN study

Désirée Van Der Heijde,Gabriella Meszaros,Francesco De Leonardis,Patrick Durez,Esperanza Naredo,Georg Schett,Inmaculada De La Torre,Douglas Schlichting,Pedro López-Romero,Roy Fleischmann,Eric Nantz,Mikkel Østergaard

doi:10.1007/s10067-018-4221-0

Abstract

The objective of this study was to evaluate structural damage progression based on clinical response in rheumatoid arthritis patients with no or limited prior disease-modifying anti-rheumatic drug treatment receiving the Janus kinase (JAK)1/JAK2 inhibitor baricitinib 4 mg, methotrexate (MTX), or the combination. Data from the phase 3 RA-BEGIN study were analysed post hoc. Proportions of patients with structural damage progression (change from baseline greater than the smallest detectable change in modified total Sharp score) at week 52 were evaluated based on sustained Disease Activity Score for 28-joint count with serum high-sensitivity C-reactive protein (DAS28-hsCRP) ≤ 3.2 or Simplified Disease Activity Index (SDAI) score ≤ 11; no formal statistical comparisons between treatments were performed to test these proportions. Baseline factors associated with risk of structural damage progression, including Clinical Disease Activity Index (CDAI) score, were identified using multivariate analysis. Patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to experience structural damage progression at week 52. In patients achieving these responses, structural damage progression was less likely with baricitinib monotherapy or plus MTX than with MTX monotherapy. In patients not achieving these sustained clinical thresholds, structural damage progression was less likely with baricitinib plus MTX than with either monotherapy. Independent of treatment, baseline factors significantly associated with increased risk of structural damage progression included higher hsCRP and CDAI score, smoking, female sex, and lower body mass index. In conclusion, patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to show structural damage progression, irrespective of treatment.

Highlights

Rheumatoid arthritis (RA) is associated with progressive and irreversible joint damage that starts early in the course of disease and can lead to disability [1]
This paper reports the results from post hoc analyses conducted using data from the RA-BEGIN study to estimate the proportion of patients with structural damage progression in each treatment group stratified by treatment response
The cut-off value of ≤ 11 for Simplified Disease Activity Index (SDAI) was that recommended by the ACR [18, 19] and EULAR [20, 21] for defining low disease activity (LDA)

Summary

Introduction

Rheumatoid arthritis (RA) is associated with progressive and irreversible joint damage that starts early in the course of disease and can lead to disability [1]. Baricitinib is an oral selective inhibitor of JAK1 and JAK2 with less effect on JAK3 and tyrosine kinase 2 [6] It has been approved in more than 40 countries, including European countries, Japan, and, recently, the USA (2 mg only), at doses of 4 or 2 mg once daily as monotherapy or in combination with methotrexate (MTX) in adults with moderate to severe RA who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs) [7, 8]. RABEGIN was a phase 3, 52-week, double-blind, three-arm, multicentre study assessing the efficacy and safety of oral baricitinib 4 mg once daily as monotherapy or in combination with MTX versus MTX monotherapy in patients with active RA who had no or limited prior DMARD treatment (NCT01711359 [9]). Further analyses were performed to clarify the effectiveness of baricitinib monotherapy with respect to structural damage progression

Objectives

Methods

Results

Conclusion