Speaker: Laura Coates
Laura Coates comments on the results of the KEEPsAKE 1 and 2 studies, and explores where risankizumab may fit in the treatment landscape for psoriatic arthritis (5.10)
So the KEEPsAKE 1 and 2 trials have looked at the efficacy and safety of risankizumab in patients with active psoriatic arthritis. And they’re the two phase III trials that will be used for registration of the drug. So the KEEPsAKE 1 trial looked in patients who were DMARD experienced but biologic naive. And the KEEPsAKE 2 study also included patients who’d had previous TNF inhibitors. And essentially both of these trials showed efficacy of risankizumab in peripheral arthritis which was the primary outcome for the study. But also in enthesitis, in dactylitis, and as we would expect given that it’s an IL-23 inhibitor, in skin psoriasis as well.
Obviously we are always happy to have additional drugs approved and having IL-23 23 inhibitors in the form of guselkumab and potentially now risankizumab for the treatment of psoriatic arthritis gives us additional options for patients with active PsA. Obviously as a new drug and a new mode of action, these drugs are coming into a relatively crowded marketplace. So we have quite a number of biologic DMARDs available for psoriatic arthritis. Although it’s clear there is still an unmet need. There are still a relatively high proportion of patients whose disease is not fully controlled and would benefit from additional treatment.
So I think the IL-23 inhibitors, including risankizumab gives us another option for treatment. I think they’re clearly particularly good for skin disease. We’ve seen that in the dermatology trials. So I think for patients with psoriatic arthritis and significant skin disease these are going to be an important option. There’s still a question about whether they will be efficacious in axial disease. So at the moment I wouldn’t use them in patients with axial disease. But I think for patients with severe skin disease they’re probably a reasonable option in psoriatic arthritis.
We have seen in the IL-23 studies that as a mode of action it does seem to be a slightly slower onset of response. So I maybe would be less likely to pick this drug in patients with very active severe disease who need a quicker fix, so to speak. But I think we do see reasonable levels of response at sort of week 24 onwards. And these drugs generally are quite well tolerated as well. So I think in terms of next steps, obviously, this gives us data on kind of initial efficacy in a mixed population, So DMARD failure patients but some biologic naive, some biologic experienced.
I think it would be useful to have more studies, particularly in those who have previously failed the TNF inhibitor. Because that’s a large cohort of our patients now and obviously a very important unmet need. It would be really interesting to start looking at how we choose biologics for different patients and really trying to optimize getting the right drug to the right patient. So thinking about the skin disease, about co-morbidities, about axial involvement, and making sure that we’re considering the efficacy in those different domains as we select treatment.
And then I think the other question really for IL-23 moving forward is whether they are going to be efficacious for axial PsA. So we’ve got good evidence of efficacy for IL-23 in skin, in peripheral joints, in enthesitis, and in dactylitis but we’ve seen a negative trial in an ankylosing spondylitis population. However, in contrast we’ve got some data from the guselkumab studies which showed that patients who had axial involvement confirmed by their physician and by some imaging showed a very significant improvement in BASDAI scores during the peripheral arthritis PsA trials.
So there’s now a question about whether this could be effective for axial psoriatic arthritis. And that may be a difference between axial PsA and a true ankylosing spondylitis population. I think that’s still a question. I personally wouldn’t choose an IL-23 inhibitor for a patient with significant axial disease at the moment because I don’t think there’s enough data and the BASDAI is obviously not a specific measure of spinal disease it will pick up improvement in other domains as well.
But I think it’s a fascinating question for the future and may also help us learn more about the pathology of the disease. In particular if the responses are different in AS compared to axial PsA. Because obviously there are significant overlaps there. But we do see some differences in terms of genetics and imaging. And this may be one of those key differences.