Effective Novel Drug for Axial Psoriatic Arthritis
PATIENTS with psoriatic arthritis, chronic inflammatory skin and joints, may also have accompanying axial symptoms. There is no clear definition of axial disease, but scientists believe there are two different phenotypes: ankylosing spondylitis phenotype and a phenotype with fewer symptoms. In the former, there is a higher prevalence of HLA-B27, a protein that is a risk factor for axial symptoms.
Phase III clinical trials analysed the efficacy of a novel antibody, guselkumab, for psoriatic arthritis with axial symptoms. Guselkumab binds to the IL-23 P19 subunit, which affects the corresponding cell pathway proven to be essential in the development of psoriatic arthritis in pre-clinical models.
Over a thousand patients with active psoriatic arthritis and swollen joints took part in the double-blind DISCOVER-1 and DISCOVER-2 trials. Patients were randomised to receive either guselkumab 100 mg every four weeks, guselkumab 100 mg every eight weeks, or a placebo in a 1:1:1 ratio.
Results showed that patients treated with guselkumab had improved symptoms of psoriatic arthritis compared to participants taking a placebo. Further to this, the safety profile showed there were no serious adverse events or deaths in patients taking guselkumab.
Following this, Philip Mease from the Swedish Medical Centre explored the effects of guselkumab on patients with axial symptoms before enrolment in the trials. The presence of HLA-B27 was measure in 190 patients; the results showed 30% was HLA-B27 positive and 70% was HLA-B27 negative.
Interestingly, patients given guselkumab had improvements in Ankylosing Spondylitis Disease Activity Scores (ASDAS). Patients also had better Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), regardless of their HLA-B27 status and this improvement was maintained at 52 weeks.
The favourable safety profile and improved ASDAS and BASDAI scores suggest that guselkumab could be an effective treatment for patients with psoriatic arthritis with axial symptoms through its unique mechanism of action.