Long-Term Safety and Efficacy of Upadacitinib in Patients with Psoriatic Arthritis: 5-Year Results from the Phase 3 SELECT-PsA 1 Study

In the phase 3 SELECT-PsA 1 study, treatment with upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, improved signs and symptoms of psoriatic arthritis (PsA) from weeks 12 through 152. We now report the long-term extension phase, evaluating safety and efficacy of upadacitinib versus adalimumab (ADA) up to week 260 (~ 5 years). Data on treatment-emergent adverse events and all primary and secondary endpoints were collected through week 260 for patients who received a placebo or ≥ 1 dose of UPA at either 15 mg (UPA15) or 30 mg (UPA30) daily, or ADA 40 mg every other week. For non-radiographic binary endpoints, both observed data and non-responder imputation methods were used, whereas for radiographic binary endpoints, the observed data method was used. For continuous endpoints, observed data and mixed-effects model repeated-measures analyses were employed. A total of 1704 patients received at least one dose of study drug, with 983 (57.7%) completing 260 weeks of treatment. The safety profile of UPA through week 260 was consistent with data from weeks 104 and 152. UPA treatment was associated with higher rates of serious infections, herpes zoster, lymphopenia, creatine kinase elevation, and non-melanoma skin cancer compared with ADA treatment. The exposure-adjusted incidence rates for major adverse cardiovascular events (n/100 PY [95% CI]: UPA15, 0.4 [0.2, 0.8]; UPA30, 0.4 [0.1, 0.9]; ADA, 0.3 [0.1, 0.7]) and venous thromboembolism (UPA15, 0.2 [0.0, 0.5]; UPA30, 0.4 [0.1, 0.9]; ADA, 0.2 [0.0, 0.6]) were low and comparable across treatment groups. Efficacy improvements observed with UPA at weeks 56 and 104 were maintained through week 260 and were comparable to those achieved with ADA. The safety profile of UPA over 5 years remained consistent with that observed at weeks 104 and 152, with no new signals identified. ClinicalTrials.gov identifier, NCT03104400. This study evaluated the effectiveness of upadacitinib, a treatment for psoriatic arthritis (PsA), over a 5-year period in comparison to the widely used drug adalimumab. A majority of patients who began treatment completed the 5-year follow-up. Upadacitinib significantly improved PsA symptoms, and its effectiveness was maintained throughout the entire study. These results were comparable to those of adalimumab; however, upadacitinib was associated with increased risk of serious infections, including life-threatening COVID-19 infection and a certain type of skin cancer, specifically non-melanoma skin cancer. To reduce the risk of infections, it is important to implement preventive measures, such as prophylactic vaccinations, and to promptly assess and treat any suspected infections. Additionally, the risk of skin cancer progression can be minimized through regular screening, thereby supporting improved outcomes through timely intervention. Serious heart problems and blood clots were rare and occurred at similar rates in both treatment groups. Overall, upadacitinib demonstrated sustained effectiveness, and its safety findings were consistent with previous publications on this study.