P127 Treating rheumatoid arthritis patients with moderate disease activity: an analysis of the upadacitinib SELECT Phase III randomised studies
Authors: Conaghan Phillip G , Pavelka Karel , Hsieh Song-Chou , Bonnington Terri-Leigh , Kent Toby C , Edwards Christopher J 
Published: April 2021

Background/Aims 

Some health systems restrict use of advanced therapies for rheumatoid arthritis (RA) to patients with high disease activity (DAS28&gt;5.1). Upadacitinib (UPA), a selective JAK inhibitor, has demonstrated significant improvement in patients with moderate-to-severe RA. We aimed to explore the efficacy and safety of UPA in RA patients with moderate disease activity.

Methods 

This was a post-hoc, subgroup analysis from three phase 3 registrational trials evaluating once daily UPA 15mg versus placebo (PBO) in patients with moderate (DAS28(CRP)&gt;3.2, ≤5.1) and high (DAS28(CRP)&gt;5.1) disease activity. Patients had prior inadequate response to csDMARDs (SELECT-COMPARE and SELECT-NEXT integrated analysis) or bDMARDs (SELECT-BEYOND). Clinical and functional outcomes were analysed at the studies primary endpoint (Week12). Missing data were handled using non-responder imputation for binary endpoints and mixed-effect model repeat measurement for continuous variables.

Results 

Across all three studies mean baseline DAS28(CRP) was ∼4.5 and ∼6.2 in moderate and severe patients, respectively. At Week 12 significantly greater proportions of csDMARD-inadequate responder (IR) and bDMARD-IR patients receiving UPA 15 mg achieved ACR20, low disease activity (DAS28(CRP)≤3.2) and remission (DAS28(CRP)&lt;2.6) compared to PBO in both disease severity subgroups (Table 1). Improvement in physical function assessed by Health Assessment Questionnaire for Rheumatoid Arthritis (HAQ-DI) and pain visual analogue scale (VAS) were significantly greater with UPA 15mg vs PBO for severe csDMARDs-IR and bDMARD-IR populations and numerically greater in moderate bDMARD-IR patients. Across all IR populations higher proportions of patients with moderate disease treated with UPA 15mg achieved DAS28(CRP)≤3.2 and DAS28(CRP)&lt;2.6 compared to those with severe disease. The safety profile of UPA in moderate and severe patients was comparable and consistent with previously published data.

Conclusion 

UPA 15mg was effective in improving clinical, functional, and patient reported outcomes in patients with either moderate or severe RA. P127 Table 1:Baseline characteristics and efficacy endpoints at week 12 from SELECT-NEXT, -COMPARE and -BEYONDTimepointKey EndpointscsDMARD IR (SELECT COMPARE and SELECT NEXT integrated)ModerateSevereUPA 15mg (n = 209)PBO (n = 195)UPA 15mg (n = 649)PBO (n = 671)BaselineAge (yrs; Mean ± SD)53.7 ± 12.654.5 ± 12.454.9 ± 11.654.1 ± 12.3Duration since diagnosis (yrs; Mean ± SD)7.5 ± 7.47.3 ± 6.78.0 ± 7.98.2 ± 8.2DAS28(CRP) (Mean ± SD)4.6 ± 0.44.6 ± 0.46.2 ± 0.76.1 ± 0.7HAQ-DI (Mean ± SD)1.2 ± 0.61.2 ± 0.61.7 ± 0.61.7 ± 0.6Pain VAS (0-100) (Mean ± SD)52.5 ± 21.448.4 ± 21.669.8 ± 18.268.9 ± 17.9Week 12ACR20 (% response, 95% CI)63.6 (57.1, 70.2)***33.8 (27.2, 40.5)71.2 (67.7, 74.7)***37.0 (33.3, 40.6)DAS28 (CRP) ≤3.2, (% response, 95% CI)61.7 (55.1, 68.3)***28.7 (22.4, 35.1)40.7 (36.9, 44.5)***10.3 (8.0, 12.6)DAS28 (CRP) ≤2.6, (% response, 95% CI)41.4 (34.5, 47.8)***14.9 (9.9, 19.9)25.1 (21.8, 28.5)***4.6 (3.0, 6.2)ΔHAQ-DI (mean, 95% CI)-0.43 (-0.51, -0.35)***-0.23 (-0.32, -0.15)-0.67 (-0.72, -0.61)***-0.31 (-0.36, -0.25)Δ Pain VAS (0-100) (% response, 95% CI)-25.0 (-28.6, -21.4)***-7.0, (-10.6, -3.2)-32.8 (-35.1, -30.5)***-16.1 (-18.4, -13.8)TimepointKey EndpointsbDMARD IR (SELECT-BEYOND)ModerateSevereUPA 15mg (n = 39)PBO (n = 38)UPA 15mg (n = 124)PBO (n = 128)BaselineAge (yrs; Mean ± SD)56.1 ± 11.157.7 ± 13.456.4 ± 11.557.6 ± 10.9Duration since diagnosis (yrs; Mean ± SD)13.6 ± 10.014.7 ± 9.411.9 ± 9.214.6 ± 9.3DAS28(CRP) (Mean ± SD)4.7 ± 0.34.4 ± 0.56.2 ± 0.86.2 ± 0.7HAQ-DI (Mean ± SD)1.4 ± 0.71.1 ± 0.51.8 ± 0.61.7 ± 0.6Pain VAS (0-100) (Mean ± SD)58.1 ± 22.449.8 ± 22.271.3 ±74.5 ±Week 12ACR20 (% response, 95% CI)61.5 (46.3, 76.8)*36.8 (21.5, 52.2)66.1 (57.8, 74.5)***26.6 (18.9, 34.2)DAS28 (CRP) ≤3.2, (% response, 95% CI)64.1 (49.0, 79.2)**28.9 (14.5, 43.4)36.3 (27.8, 44.8)***9.4 (4.3, 14.4)DAS28 (CRP) ≤2.6, (% response, 95% CI)43.6 (28.0, 59.2)*21.1 (8.1, 34.0)24.2 (16.7, 31.7)***6.3 (2.1, 10.4)ΔHAQ-DI (mean, 95% CI)-0.24 (-0.41, -0.07)-0.12 (-0.30, 0.05)-0.47 (-0.56, -0.37)***-0.18 (-0.28, -0.08)Δ Pain VAS (0-100) (% response, 95% CI)-16.8 (-25.4, -8.1)-5.4 (-14.3, 3.4)-28.7 (-33.5, -24.0)***-12.2 (-17.0, -7.3)*p ≤ 0.05;**p ≤ 0.01;***p ≤ 0.001 for comparison of UPA versus PBO.

Disclosure 

P.G. Conaghan: Other; P.C. has been a consultant or speaker for AbbVie, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer. K. Pavelka: Other; K.P. has received honoraria for consultations and lectures from AbbVie, Roche, Pfizer, MSD, Sanofi, UCB and Amgen. S. Hsieh: None. T. Bonnington: Other; T.B. is an employee at AbbVie Limited. T.C. Kent: Other; T.C. is an employee at AbbVie Limited. C.J. Edwards: Other; C.E. has received honoraria, advisory boards, speakers bureau, research support from AbbVie, BMS, Biogen, Fresenius, Gilead Janssen, Lilly, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB.