Upadacitinib (RINVOQ), an oral selective second-generation Janus kinase (JAK)1 inhibitor, is used to treat moderate to severe rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, and severe atopic dermatitis, particularly in patients who have not responded adequately to other treatments. Upadacitinib is accompanied by a boxed warning of increased risk of cardiovascular events and serious infections. Upadacitinib offers a more favorable safety profile than its rival, such as Pfizer's XELJANZ (tofacitinib), because of its capacity to have modest effects on JAK3. In the first quarter of 2024, its total revenue came around USD 1.1 billion, up 59.3% from the previous year mostly because of the high demand for its products in the US among psoriatic arthritis sufferers.

Axial Spondyloarthritis

POS0050: Upadacitinib's Efficacy and Safety in Active Non-radiographic Axial spondyloarthritis (nr-axSpA) 2-Year Phase III SELECT-AXIS 2 Study Results

Of 314 patients randomized at study entry, 271 entered the LTE (continuous upadacitinib, n=133;  placebo (PBO) to upadacitinib, n=138), and 76.1% completed 104 weeks (continuous upadacitinib, n=123; placebo to upadacitinib, n=116). Upadacitinib demonstrated sustained efficacy in treating active nr-axSpA through week 104, with continuous upadacitinib showing consistent response rates for ASAS40, ASDAS low disease activity (LDA), and inactive disease (ID) and improvements in back pain and quality of life measures. Patients who switched from placebo to upadacitinib also experienced gradual improvements, although slightly lower than continuous upadacitinib. Mean changes from BL to Week 104 in MRI SPARCC spine scores were -0.72 and -0.47 in the continuous upadacitinib group and the placebo to upadacitinib group, respectively; sacroiliac joint scores were -2.33 and -2.30. The low rates of radiographic progression and favorable safety profile of upadacitinib further highlight its potential to impact the treatment landscape for nr-axSpA positively. Rates of serious adverse events (AEs) and AEs leading to discontinuation of the study drug were 8.7 and 5.3 events/100 patient-years, respectively, and no deaths occurred. These findings suggest that upadacitinib could become a valuable option for patients with nr-axSpA, offering sustained efficacy and manageable safety over the long term, potentially reshaping the approach to managing this condition.

POS0798: Efficacy, Safety, and Radiographic Outcomes in Active Ankylosing Spondylitis: 2-Year Data from Phase III SELECT-AXIS 2 Study of Upadacitinib

Of 420 randomized patients who received the study drug (continuous upadacitinib: n=211; placebo to upadacitinib: n=209), 331 (78.8%) completed 104 weeks of treatment (n=163 and n=168, respectively). Upadacitinib demonstrated sustained efficacy in treating active ankylosing spondylitis up to Week 104, with similar responses between continuous upadacitinib and placebo to upadacitinib groups. Disease activity measures, including ASAS40, ASDAS, back pain, and functional outcomes, showed significant improvements. MRI inflammation and radiographic progression rates were low, indicating upadacitinib's efficacy in managing AS symptoms and structural damage. Upadacitinib's safety profile remained favorable, with no new safety concerns identified. These findings support upadacitinib 15 mg as a viable treatment option for biologic disease-modifying antirheumatic drugs (bDMARDs) inadequate responders with active ankylosing spondylitis, offering sustained efficacy and manageable safety over the long term.

Conclusion: Upadacitinib demonstrates sustained efficacy in treating active nr-axSpA and ankylosing spondylitis for up to 2 years, with manageable safety profiles and low rates of radiographic progression. It offers significant improvements in disease activity, back pain, and quality of life measures, making it a valuable treatment option for patients with these conditions.

Psoriatic Arthritis

POS0978: Upadacitinib and Adalimumab Show Superior Pain Reduction in PsA Patients: A 16-Week Comparative Study

In a study involving 1281 patients with PsA, upadacitinib (n=429) and adalimumab (n=429) significantly improved pain compared to placebo (n=423) by week 16. Patient Global Assessment (PtGA) of pain scores improved more with upadacitinib (-25.0) and adalimumab (-23.0) than with placebo (-11.0). Both treatments showed significantly greater total and direct effects on pain improvement compared to placebo. Upadacitinib exhibited numerically greater reductions in total pain effects than adalimumab. Additionally, upadacitinib and adalimumab significantly reduced elicited pain assessed as TJC28 (tender joint count for 28 joints) compared to placebo, with upadacitinib showing numerically greater reductions than adalimumab. These findings indicate that upadacitinib and adalimumab produce substantial pain improvements via inflammatory and non-inflammatory mechanisms, with upadacitinib demonstrating slightly superior efficacy.

POS0945: Long-Term Efficacy and Safety of Upadacitinib in Moderate to Severe Psoriatic Arthritis: 152-Week Data from the SELECT-PsA 1 and 2 Trials

The analysis of PsA patients treated with upadacitinib 15 mg or adalimumab demonstrated sustained responses in those achieving ACR50, ACR70, PASI75, and PASI90 at Week 24. In upadacitinib 15 mg treated patients who achieved ACR50 at Week 24, most patients sustained the response at Week 152 (non bDMARDs–IR, 88.1%; bDMARD-IR, 78.1%). Similar results occurred for non–bDMARD–IR and bDMARD-IR, respectively, in ACR70 (77.7% and 81.8%), PASI75 (80.8% and 82.5%), and PASI90 (75.0% and 66.7%; Comparable maintenance of response was observed between upadacitinib 15 mg and adalimumab in SELECT-PsA 1, indicating durable disease control with upadacitinib 15 mg over nearly three years in both non-bDMARD-IR and bDMARD-IR PsA patients. Although this analysis focused on Week 24 responders who continued the trials, it highlights the potential for long-term efficacy with upadacitinib 15 mg in PsA management. Future studies utilizing continuous endpoints can further substantiate these findings.

Conclusion: Upadacitinib and adalimumab demonstrate superior pain reduction in PsA patients compared to placebo, with upadacitinib showing slightly better efficacy. Additionally, upadacitinib exhibits sustained responses in PsA patients over nearly three years, indicating its potential as a long-term treatment option for PsA management.