Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: pooled results through week 52 of two phase III, randomised, placebo-controlled studies

Abstract

Objectives: To evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.

Methods: Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.

Results: Baseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.

Conclusions: Guselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.

Trial registration numbers: NCT03162796, NCT03158285.

Keywords: arthritis, psoriatic; biological therapy; therapeutics.

Conflict of interest statement

Competing interests: CTR has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB Pharma; and speaker fees from Novartis, Pfizer and UCB Pharma. PJM has received research grants, consulting fees and/or speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma and UCB Pharma. W-HB has received consulting fees from AbbVie, Almirall, Bristol Myers Squibb, Celgene, Lilly, Janssen, Leo, Novartis and UCB Pharma; speaker fees from AbbVie, Almirall, Janssen, Leo and UCB Pharma; fees for expert testimony from Novartis; and fees for participation on an advisory board from AbbVie, Almirall, Janssen, Leo, Novartis and UCB Pharma. JT has received research grants from AbbVie, Amgen, Bristol Myers Squibb, Celgene, CoreVitas, Lilly, Gilead, Janssen, Pfizer and Sun Pharma; consulting fees from AbbVie, Lilly, Janssen, Novartis and Pfizer; speaker fees from AbbVie, Amgen, Bristol Myers Squibb, Lilly, Janssen and Pfizer; and advisory board fees from Bristol Myers Squibb, Lilly, Gilead, Janssen, Novartis and Pfizer. ES has received research grants and consulting fees from Janssen. SDC is an employee of Janssen Scientific Affairs, LLC and owns stock in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly owned subsidiary. APK, XLX, SS and SX are employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary. MS is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson and owns stock in Johnson & Johnson. YJ is a consultant employed by Cytel, Inc and funded by Janssen to provide statistical support. YW is a consultant employed by IQVIA, Inc and funded by Janssen to provide statistical support. JFM has received consulting fees from AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Janssen, Lilly, Novartis, Pfizer, Sun Pharma and UCB Pharma. IBM has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Causeway Therapeutics, Gilead, Janssen, Lilly, Novartis, Pfizer, Regeneron and Sanofi; has served as a board member for NHS Greater Glasgow & Clyde; has served as Vice Principal & Head of MVLS College at University of Glasgow; and has received research grants from AbbVie, Amgen, Bristol Myers Squibb, Causeway Therapeutics, Lilly, Gilead, Janssen, Novartis and Pfizer. AD has received consulting fees from AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB Pharma; speaker fees from Janssen, Novartis, Pfizer and UCB Pharma; and advisory board fees from AbbVie, GlaxoSmithKline, Janssen, MoonLake, Novartis and UCB Pharma.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Proportions of patients achieving ACR20 response at week 24 and week 52 by patient demographics, disease characteristics and csDMARD use at baseline. Week 24 response rates (NRI) are compared between guselkumab (GUS) and placebo (PBO) via ORs and 95% CIs (depicted via forest plot; actual values provided in online supplemental table 1). Week 52 response rates (NRI) for GUS Q4W and Q8W were determined to assess durability of ACR20 response rates within each patient subgroup. Prior to week 24, patients meeting treatment failure criteria were considered non-responders. Missing data through weeks 24 and 52 were imputed as non-response. ACR20, American College of Rheumatology 20% improvement; BMI, body mass index; CI, confidence interval; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; MTX, methotrexate; NRI, non-responder imputation; OR, odds ratio; PsA, psoriatic arthritis; Q4W/Q8W, every 4 weeks/every 8 weeks.

Figure 2

Proportions of patients achieving (A) ACR50 and (B) ACR70 responses at week 24 and week 52 by patient demographics, disease characteristics and csDMARD use at baseline. Week 24 response rates (NRI) are compared between guselkumab (GUS) and placebo (PBO) via ORs and 95% CIs (depicted via forest plot; actual values provided in online supplemental table 1). Week 52 response rates (NRI) for GUS Q4W and GUS Q8W were determined to assess durability of ACR50 and ACR70 response rates within each patient subgroup. Prior to week 24, patients meeting treatment failure criteria were considered non-responders. Missing data through Weeks 24 and 52 were imputed as non-response. ACR50/70, American College of Rheumatology 50/70% improvement; BMI, body mass index; CI, confidence interval; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; MTX, methotrexate; NRI, non-responder imputation; OR, odds ratio; PsA, psoriatic arthritis; Q4W/Q8W, every 4 weeks/every 8 weeks.

Figure 3

Proportions of patients with ≥3% BSA with PsO and IGA ≥2 at baseline achieving an (A) IGA 0/1 response (IGA psoriasis score of 0 (cleared) or 1 (minimal) and ≥2-grade reduction from baseline) and (B) IGA 0 response (IGA psoriasis score of 0) at week 24 and week 52 by patient demographics, disease characteristics, and csDMARD use at baseline. Week 24 response rates (NRI) are compared between guselkumab (GUS) and placebo (PBO) via ORs and 95% CIs (depicted via forest plot; actual values provided in online supplemental table 2). Week 52 response rates (NRI) for GUS Q4W and GUS Q8W were determined to assess durability of IGA 0/1 and IGA 0 response rates within each patient subgroup. Prior to week 24, patients meeting treatment failure criteria were considered non-responders. Missing data through weeks 24 and 52 were imputed as non-response. *Plot is undrawable due to NC values. BMI, body mass index; BSA, body surface area; CI, confidence interval; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; IGA, Investigator’s Global Assessment; MTX, methotrexate; NC, no count; NRI, non-responder imputation; OR, odds ratio; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis; Q4W/Q8W, every 4 weeks/every 8 weeks.

Figure 4

Proportions of patients achieving (A) FACIT-Fatigue response (≥4-point improvement in FACIT-F score from baseline) and (B) HAQ-DI response (≥0.35-point improvement in HAQ-DI score from baseline among patients with a HAQ-DI score ≥0.35 at baseline) at week 24 and week 52 by patient demographics, disease characteristics and csDMARD use at baseline. Week 24 response rates (NRI) are compared between guselkumab (GUS) and placebo (PBO) via ORs and 95% CIs (depicted via forest plot; actual values provided in online supplemental table 3). Week 52 response rates (NRI) for GUS Q4W and GUS Q8W were determined to assess durability of FACIT-F and HAQ-DI response rates within each patient subgroup. Prior to week 24, patients meeting treatment failure criteria were considered non-responders. Missing data through weeks 24 and 52 were imputed as non-response. BMI, body mass index; CI, confidence interval; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire Disability Index; MTX, methotrexate; NRI, non-responder imputation; OR, odds ratio; PsA, psoriatic arthritis; Q4W/Q8W, every 4 weeks/every 8 weeks.

Figure 5

Proportions of patients achieving (A) PASDAS Low Disease Activity (PASDAS score ≤3.2) and (B) MDA responses at week 24 and week 52 by patient demographics, disease characteristics and DMARD use at baseline. Week 24 response rates (NRI) are compared between guselkumab (GUS) and placebo (PBO) via ORs and 95% CIs (depicted via forest plot; actual values provided in online supplemental table 4). Week 52 response rates (NRI) for GUS Q4W and GUS Q8W were determined to assess durability of PASDAS LDA and MDA response rates within each patient subgroup. Prior to week 24, patients meeting treatment failure criteria were considered non-responders. Missing data through weeks 24 and 52 were imputed as non-response. *Plot is not drawable due to NC values. BMI, body mass index; BSA, body surface area; CI, confidence interval; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; LDA, low disease activity; MDA, minimal disease activity; MTX, methotrexate; NC, no count; NRI, non-responder imputation; OR, odds ratio; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis; Q4W/Q8W, every 4 weeks/every 8 weeks.