Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program

Abstract

Objectives: To evaluate the inhibition of progression of structural joint damage through week 48 in patients with moderately to severely active RA receiving upadacitinib as monotherapy or in combination with MTX.

Methods: Radiographic progression was assessed in two phase 3 randomized controlled trials. MTX-naïve patients were randomized to upadacitinib 15 or 30 mg once daily or MTX monotherapy (SELECT-EARLY, n = 945), while MTX inadequate responders (IRs) were randomized to upadacitinib 15 mg once daily or adalimumab 40 mg every other week or placebo added to background MTX (SELECT-COMPARE, n = 1629). The mean changes from baseline in modified total Sharp score (mTSS), joint space narrowing and erosion scores were determined. Data were analysed both by linear extrapolation for missing data imputation and treatment switching and as observed.

Results: In patients naïve or with limited exposure to MTX (SELECT-EARLY), mean changes from baseline to week 48 in mTSS were 0.03 for upadacitinib 15 mg, 0.14 for upadacitinib 30 mg and 1.00 for MTX based on linear extrapolation (P < 0.001 for both upadacitinib doses vs MTX). Among patients with an inadequate response to MTX (SELECT-COMPARE), the mean change from baseline in mTSS was significantly reduced in the upadacitinib 15 mg plus MTX group vs placebo plus MTX (0.28 vs 1.73; P < 0.001). The mean change from baseline in the adalimumab plus MTX group was 0.39.

Conclusion: Upadacitinib monotherapy or in combination with background MTX was effective in inhibiting the progression of structural joint damage through week 48 in MTX-naïve and MTX-IR patients with RA.

Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT02706873 and NCT02629159.

Keywords: DMARDs; biological therapies; outcome measures; radiology; rheumatoid arthritis.

Fig. 1

Change from baseline in mTSS in the (A) LE and (B) as-observed analyses over 1 year In SELECT-COMPARE, at week 26 (6-month visit), patients receiving placebo were switched to upadacitinib. The month 6 analysis was conducted at week 24 in SELECT-EARLY and week 26 in SELECT-COMPARE; the year 1 analysis was conducted at week 48 in both studies. eow, every other week; PBO, placebo; UPA, upadacitinib. ***P < 0.001 upadacitinib vs MTX or placebo. ^###P < 0.001 and ^#P < 0.05 adalimumab vs placebo.

Fig. 2

Percentage of non-progressors at (A) 6 months and (B) 1 year LE and as-observed analyses. Non-progressor defined as a patient with a change from baseline in mTSS ≤0. In SELECT-COMPARE, at week 26 (6-month visit), patients receiving placebo were switched to upadacitinib. The month 6 analysis was conducted at week 24 in SELECT-EARLY and week 26 in SELECT-COMPARE; the year 1 analysis was conducted at week 48 in both studies. eow, every other week. ***P < 0.001 upadacitinib vs MTX or placebo; ^###P < 0.001 adalimumab vs placebo.

Fig. 3

Cumulative probability plots of mean change in mTSS in the (A) LE and (B) as-observed analyses The 1-year analysis. In SELECT-COMPARE, at week 26 (6-month visit), patients receiving placebo were switched to upadacitinib. eow: every other week.

Fig. 4

Change from baseline in (A, B) joint-space narrowing and (C, D) erosion scores The (A and C) LE and (B and D) as-observed analyses. In SELECT-COMPARE, at week 26 (6-month visit), patients receiving placebo were switched to upadacitinib. The month 6 analysis was conducted at week 24 in SELECT-EARLY and week 26 in SELECT-COMPARE; the year 1 analysis was conducted at week 48 in both studies. eow: every other week; ES: erosion score; JSN: joint-space narrowing score; PBO: placebo; UPA: upadacitinib. ***P < 0.001, **P < 0.01, *P < 0.05 upadacitinib vs MTX or placebo. ^###P < 0.001 and ^##P < 0.01 adalimumab vs placebo.

Fig. 5

Change in (A) mTSS, (B) joint-space narrowing, (C) erosion score and (D) percentage of non-progressors Analyses among non-switchers in the SELECT-EARLY and SELECT COMPARE (as-observed analysis). SELECT-EARLY at 6 months: MTX, n = 232; upadacitinib 15 mg, n = 263; upadacitinib 30 mg, n = 266; and at 1 year: MTX, n = 215; upadacitinib 15 mg, n = 249; upadacitinib 30 mg, n = 255. SELECT-COMPARE at 6 months: upadacitinib 15 mg, n = 348; adalimumab 40 mg, n = 136; and at 1 year: upadacitinib 15 mg, n = 342; adalimumab 40 mg, n = 132. Non-switchers were patients who remained on randomized therapy. eow: every other week; ES: erosion score; JSN: joint-space narrowing score; PBO: placebo; UPA: upadacitinib.