Upadacitinib monotherapy improves patient-reported outcomes in rheumatoid arthritis: results from SELECT-EARLY and SELECT-MONOTHERAPY

Abstract

Objective: To evaluate the effect of upadacitinib (UPA) monotherapy vs MTX on patient-reported outcomes (PROs) in patients with RA who were MTX-naïve or who had an inadequate response to MTX (MTX-IR).

Methods: PROs from the SELECT-EARLY and SELECT-MONOTHERAPY randomized controlled trials were evaluated at Weeks 2 and 12/14. Patients were ≥18 years of age with RA symptoms for ≥6 weeks (SELECT-EARLY, MTX-naïve) or diagnosed RA for ≥3 months (SELECT-MONOTHERAPY, MTX-IR) and received UPA monotherapy (15 or 30 mg) or MTX. PROs included Patient Global Assessment of Disease Activity (PtGA), pain visual analogue scale, HAQ Disability Index (HAQ-DI), morning stiffness duration/severity, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (SELECT-EARLY), health-related quality of life (HRQOL) by the 36-iem Short Form Health Survey and Work Productivity and Activity Impairment (WPAI; SELECT-EARLY). Least square mean (LSM) changes and proportions of patients reporting improvements greater than or equal to the minimum clinically important differences and normative values were determined.

Results: In 945 MTX-naïve and 648 MTX-IR patients, UPA monotherapy (15 mg, 30 mg) vs MTX resulted in greater reported LSM changes from baseline at Weeks 12/14 in PtGA, pain, HAQ-DI, morning stiffness duration/severity, FACIT-F (SELECT-EARLY), HRQOL and WPAI (SELECT-EARLY). These changes were statistically significant with both doses of UPA vs MTX at Weeks 12/14 in both RCTs. Improvements were reported as early as week 2. Compared with MTX, more UPA-treated MTX-naïve and MTX-IR patients reported improvements greater than or equal to the minimum clinically important differences and scores greater than or equal to normative values.

Conclusion: Among MTX-naïve and MTX-IR patients with active RA, UPA monotherapy at 15 or 30 mg for 12/14 weeks resulted in statistically significant and clinically meaningful improvements in pain, physical function, morning stiffness, HRQOL and WPAI compared with MTX alone.

Clinical trial registration number: SELECT-EARLY (NCT02706873) and SELECT-MONOTHERAPY (NCT02706951) are registered with ClinicalTrials.gov.

Keywords: DMARDs; RA; inflammation; outcome measures; quality of life.

Fig. 1

Change in SF-36 domain over time relative to age- and gender-matched normative values (A) SF-36 domain scores at baseline and week 12 in MTX-naïve patients vs age- and gender-matched normative values. (B) SF-36 domain scores at baseline and week 14 in MTX-IR patients vs age- and gender-matched normative values. A/G, age/gender; BL, baseline; BP, bodily pain; GH, general health; MH, mental health; MTX-IR, inadequate response to MTX; PF, physical functioning; RE, role-emotional; RP, role-physical; SF, social functioning; SF-36, 36-Item Short Form Health Survey; UPA, upadacitinib; VT, vitality; Wk, week.

Fig. 2

Patients reporting PRO score improvements greater than or equal to the MCID at week 12 or 14 (A) Percentage of MTX-naïve patients reporting PRO scores greater than or equal to the MCID at week 12. (B) Percentage of MTX-IR patients reporting PRO scores greater than or equal to the MCID at week 14. AM, morning; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue; HAQ-DI, Health Assessment Questionnaire Disability Index; MCID, minimum clinically important difference; MCS, Mental Component Summary; MTX-IR, inadequate response to MTX; NNT, number needed to treat; PCS, Physical Component Summary; PRO, patient-reported outcome; PtGA, Patient’s Global Assessment of Disease Activity; SF-36, 36-Item Short Form Health Survey; UPA, upadacitinib; VAS, visual analogue scale; WPAI, Work Productivity and Activity Impairment Questionnaire.

Fig. 3

Patients reporting SF-36 domain score improvements greater than or equal to the MCID at week 12 or 14 (A) Percentage of MTX-naïve patients reporting SF-36 domain scores greater than or equal to the MCID at week 12. (B) Percentage of MTX-IR patients reporting SF-36 domain scores greater than or equal to the MCID at week 14. BP, bodily pain; GH, general health; MCID, minimum clinically important difference; MH, mental health; MTX-IR, inadequate response to MTX; NNT, number needed to treat; PF, physical functioning; RE, role-emotional; RP, role-physical; SF, social functioning; SF-36, 36-Item Short Form Health Survey; UPA, upadacitinib; VT, vitality.