Early Remission with Targeted Therapies Linked to Better Health Outcomes in Rheumatoid Arthritis

Laure Gossec, MD, PhD

Credit: LinkedIn

Findings from a recent study are providing clinicians with an overview of the impact of achieving early remission on health outcomes in patients with rheumatoid arthritis (RA) treated with upadacitinib or adalimumab following an inadequate response to methotrexate.¹

Patients who achieved early remission with upadacitinib or adalimumab had less subsequent pain and fatigue as well as better physical function and physical quality of life (QoL) for > 1 year compared to patients who did not reach early remission.¹

“Currently, there is evidence indicating that early remission is associated with clinical and functional benefits in early RA patients using conventional synthetic disease-modifying antirheumatic drugs; however, the association between early attainment of remission after addition of targeted therapy to conventional synthetic disease-modifying antirheumatic drug and any clinical, functional, or QoL benefits in patients with RA remains unclear,” Laure Gossec, MD, PhD, professor of rheumatology at Sorbonne University and Pitie-Salpetriere Hospital, and colleagues wrote.¹

An inflammatory, autoimmune condition that can affect the joints and organs, RA symptoms often spread to larger joints as the disease progresses and is subsequently associated with high disease burden and impaired QoL. Although there is no cure for RA, remission of symptoms is more likely when treatment begins early with disease-modifying antirheumatic drugs.²

To better understand the benefits of achieving early remission, investigators assessed the association between early remission, defined as Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) <2.6 at week 12 following upadacitinib or adalimumab initiation, with outcomes such as pain, physical function, fatigue, and QoL in patients with RA with inadequate response to methotrexate. Using data collected from the phase 3 SELECT-COMPARE trial, investigators conducted a post-hoc analysis of participants randomly assigned to upadacitinib or adalimumab.¹

Mean change from baseline and the proportion of patients who reached minimum clinical important differences and normative cut-off scores were evaluated for the following outcomes:

• Pain on visual analog scale
• Physical function, measured using Health Assessment Questionnaire – Disability Index (HAQ-DI)
• QoL, measured using Short form–36 Physical and Mental Component Summary scores
• Fatigue, measured using Functional Assessment of Chronic Illnesses Therapy-Fatigue (FACIT-Fatigue)
• Patient’s Global Assessment (PtGA) and Physician’s Global Assessment (PhGA)
• Swollen and tender joint counts.

Outcomes for patients who achieved early remission versus those who did not were compared at weeks 26, 48, 156, and 252.¹

Of 885 patients included in the analysis, 28% (n = 247) reached early remission at week 12. Investigators noted significantly greater improvements from baseline were observed for all outcomes at week 26 in patients who achieved early remission compared with those who did not after linear/logistic regression adjustment for baseline characteristics.¹

Upon analysis, early remission was associated with significantly greater odds (adjusted odds ratio [aOR] range, 2.9–5.1) of achieving meaningful improvements in HAQ-DI, fatigue, pain, PtGA, and physical QoL (SF-36 PCS) for at least 48 weeks. Patients in early remission also had significantly greater odds (aOR, 2.4–3.5) of achieving meaningful improvements in HAQ-DI, pain, and PtGA for a minimum of 252 weeks. However, there were no significant differences between patients who achieved early remission and those who did not for improvement in mental QoL.¹

Regarding normative values, investigators pointed out a greater percentage of patients who achieved early remission had scores comparable to the general population for physical and mental QoL, HAQ-DI, and fatigue for a minimum of 48 weeks. Additionally, patients in the early remission group had zero swollen and tender joint counts for up to 252 weeks.¹

Investigators observed a reduction in the mean change difference between groups and odds ratios over time, something they attributed to some patients in the non-remission group at week 12 achieving remission at later time points.¹

“This post-hoc analysis demonstrated that patients with moderately to severely active RA and an inadequate response to methotrexate, who were treated with either upadacitinib or adalimumab and achieved early remission, had less subsequent pain, and fatigue, as well as better physical function and physical QoL for at least 1 year vs patients who did not reach early remission,” investigators concluded.¹ “Thus, achieving remission early was associated with better health outcomes in patients with RA using targeted therapies.”

References:

1. ^{Gossec L, Patel J, Kadakia A, et al. POS0643 ASSOCIATION OF EARLY REMISSION ON CLINICAL AND PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS: POST-HOC ANALYSIS OF DATA FROM THE SELECT-COMPARE STUDY. Annals of the Rheumatic Diseases 2024;83:776-777. https://doi.org/10.1136/annrheumdis-2024-eular.1469}
2. ^{Mayo Clinic. Rheumatoid Arthritis. Diagnosis and Treatment. January 25, 2023. Accessed June 21, 2024. https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/diagnosis-treatment/drc-20353653}