Should we be using JAKi more in female SpA patients? Save

In recent years, data has emerged suggesting that female patients with spondyloarthritis, both psoriatic arthritis and axial spondyloarthritis, may have worse outcomes than male patients. A number of post-hoc analyses of randomised controlled trials of both TNF inhibitors and IL-17 inhibitors suggest that this phenomenon is also manifested in the responses to these agents; female patients do less well than male patients. The mechanisms behind this remain to be fully elucidated. A number of potential possibilities have been suggested, including an over-representation of non-inflammatory symptoms, a real reduced response rate to these agents in females, and deficiencies in how we measure disease activity resulting in a falsely lower response.

Two studies presented at Sunday’s “Spondyloarthritis including Psoriatic Arthritis – Treatment poster 1 session” were intriguing given this background. These looked at response rates in male and female patients treated with upadacitinib in axial spondyloarthritis and psoriatic arthritis respectively.

The first poster, #0589, was presented by Sofia Ramiro and looked at the axial spondyloarthritis population from the SELECT-AXIS 1 and 2 trials. The bottom line of this study is initially surprising given what we have seen with other agents. There was no significant difference in outcomes at week 14 or week 52 for male and female patients treated with upadacitinib. However there were numerical differences that while small were relatively consistent across groups. In bDMARD-naïve r-axSpA, ASAS40 at week 14 was achieved by 43% of female and 56% of male patients, and ASDAS LDA by 43% of female and 52% of male patients. In bDMARD-IR r-axSpA, ASAS40 at week 14 was achieved by 35% of female and 48% of male patients, and ASDAS LDA by 28% of female and 50% of male patients. In nr-axSpA ASAS40 was achieved at week 14 by 32% of female and 63% of male patients, and at week 52 by 60% of female and 67% of male patients. ASDAS LDA was achieved by 33% of female and 55% of male patients at week 14, and 52% of female and 62% of male patients at week 52.

The second poster, #0557, by Lihi Eder and colleagues looked at the psoriatic arthritis patients from the SELECT-PsA 1 and 2 studies. In SELECT-PsA 1, 74% of male and 68% of female patients treated with upadacitinib achieved ACR20 at week 12. This contrasted with 77% of male and 54% of female patients treated with adalimumab in the same study. In SELECT-PsA 2, 61% of male and 53% of female patients achieved ACR20 at week 12. At week 24, ACR20 responses in SELECT-PsA 1 were 81% vs 68% for male vs female upadacitinib treated, and 79% vs 56% for adalimumab treated. In SELECT-PsA 2 week24 ACR20 was 59% in both males and females.

Where does this data leave us?

The message appears clearer in PsA, female patients appear to have closer response to their male counterparts when upadacitinib is the advance therapy used. The situation in ax-SpA is less clear, with the suggestion that there may be residual differences, although it is possible that these may be less marked than we see with bDMARDs. Any potential prioritisation of JAKi as a treatment option must be balanced against possible safety concerns however.