Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

Abstract

Background: In SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1.

Methods: Patients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised.

Results: Consistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.

Conclusion: Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

Keywords: adalimumab; arthritis; psoriatic; tumor necrosis factor inhibitors.

Figure 1

Proportions of patients achieving (A) ACR20, (B) ACR50 and (C) ACR70 response over 56 weeks (NRI). ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology response criteria; ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; EOW, every other week; NRI, non-responder imputation; PBO, placebo; QD, once daily; UPA, upadacitinib. Patients originally randomised to placebo switched to either upadacitinib 15 mg QD or upadacitinib 30 mg QD (1:1) at week 24 and their data up to week 24 are under placebo exposure. 95% CIs for response rate were calculated based on normal approximation to the binominal distribution. Nominal p value was constructed using Cochran-Mantel-Haenszel test adjusted for the main stratification factor of current DMARD use (yes/no).

Figure 2

Proportions of patients achieving (A) ACR20, (B) ACR50 and (C) ACR70 response at weeks 12, 24 and 56 (NRI). Nominal p values are for upadacitinib versus adalimumab. ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology response criteria; ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; EOW, every other week; NRI, non-responder imputation; PBO, placebo; QD, once daily; UPA, upadacitinib. For the week 56 data, patients originally randomised to placebo switched to either upadacitinib 15 mg QD or upadacitinib 30 mg QD (1:1) at week 24 and their data up to week 24 are under placebo exposure. 95% CIs for response rate were calculated based on normal approximation to the binominal distribution. Nominal p value was constructed using Cochran-Mantel-Haenszel test adjusted for the main stratification factor of current DMARD use (yes/no).

Figure 3

(A) Change from baseline at week 56 in radiographic endpoints. (B) Probability plot of change from baseline in mTSS at week 56 (linear extrapolation). Nominal p values are for upadacitinib versus placebo. ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; EOW, every other week; JSN, joint space narrowing score; mTSS, modified total Sharp/van der Heijde Score; PBO, placebo; QD, once daily; UPA, upadacitinib. Patients originally randomised to placebo switched to either upadacitinib 15 mg QD or upadacitinib 30 mg QD (1:1) at week 24 and their data up to week 24 are under placebo exposure. Least square mean and 95% CIs and nominal p values are based on an analysis of covariance model including treatment and the stratification factor current DMARD use (yes/no) as fixed factors and baseline value as covariate.

Figure 4

Proportion of patients achieving MDA over 56 weeks (NRI). Nominal p values are for upadacitinib versus adalimumab. ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; EOW, every other week; MDA, minimal disease activity; NRI, non-responder imputation; PBO, placebo; QD, once daily; UPA, upadacitinib. Patients originally randomised to placebo switched to either upadacitinib 15 mg QD or upadacitinib 30 mg QDy (1:1) at week 24 and their data up to week 24 are under placebo exposure. NRI with additional rescue handling was used, where patients rescued at week 16 are imputed as non-responders. 95% CIs for response rate were calculated based on normal approximation to the binominal distribution. Nominal p value was constructed using Cochran-Mantel-Haenszel test adjusted for the main stratification factor of current DMARD use (yes/no).

Figure 5

Proportion of patients achieving (A) PASI75, (B) PASI90, (C) PASI100 and (D) sIGA 0/1 response over 56 weeks (NRI). Nominal p values are for upadacitinib versus adalimumab. ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; EOW, every other week; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area Severity Index; PBO, placebo; QD, once daily; sIGA, Static Investigator Global Assessment of Psoriasis; UPA, upadacitinib. After week 16 assessments have been performed, patients may use concomitant treatments specifically for psoriasis per investigator judgement. Patients originally randomised to placebo switched to either upadacitinib 15 mg QD or upadacitinib 30 mg QD (1:1) at week 24 and their data up to week 24 are under placebo exposure. 95% CIs for response rate were calculated based on normal approximation to the binominal distribution. Nominal p value was constructed using Cochran-Mantel-Haenszel test adjusted for the main stratification factor of current DMARD use (yes/no).

Figure 6

(A) Exposure-adjusted event and (B) incidence rates of treatment-emergent AEs through week 56. ^aExcluding tuberculosis and herpes zoster. ADA, adalimumab; AE, adverse event; CPK, creatine phosphokinase; EAER, exposure-adjusted event rate; EAIR, exposure-adjusted incidence rate; EOW, every other week; GI, gastrointestinal; MACE, major adverse cardiovascular events (defined as non-fatal myocardial infarction, non-fatal stroke and cardiovascular death); NMSC, non-melanoma skin cancer; PY, patient years; QD, once daily; UPA, upadacitinib; VTE, venous thromboembolism (defined as deep vein thrombosis and pulmonary embolism). There were 11 malignancies reported in each of the upadacitinib 15 mg (4 basal cell carcinomas, 2 squamous cell carcinoma of skin and 1 event each of endometrial adenocarcinoma, lung adenocarcinoma, lung cancer metastatic, malignant melanoma and neuroendocrine carcinoma) and upadacitinib 30 mg groups (2 basal cell carcinomas, 2 squamous cell carcinoma of skin and 1 event each of adenocarcinoma of colon, Bowen’s disease, breast cancer, clear cell renal cell carcinoma, invasive breast carcinoma, lung adenocarcinoma and plasma cell myeloma), and six malignancies reported with adalimumab (two basal cell carcinomas and one event each of colon cancer metastatic, ovarian cancer, pancreatic carcinoma metastatic and uterine cancer).