Medicine Matters rheumatology

The EXCEED trial is a head-to-head trial of secukinumab versus TNF inhibitor adalimumab map to look particularly for superior efficacy in the musculoskeletal domain. So we've been asking for many years for head-to-head trials in psoriatic arthritis, and whilst these have been more common in psoriasis studies, we haven't really seen them in psoriatic arthritis.

And there's been a lot of discussion about how those trials should be designed, really. So the previous study, which looked at ixekizumab versus adalimumab used a combination of a skin and joint endpoint. And that showed superiority over adalimumab, driven particularly by the fact that the skin responses were better.

However, in EXCEED, the primary outcome was the ACR 20. So it was a measure just of musculoskeletal disease, not taking into account the skin psoriasis. It's a head-to-head trial of patients who are biologic naive, and they are randomized to either of the two drugs but using the higher dose of secukinumab, the 300 milligram dose of secukinumab.

So they EXCEED trial failed to meet its primary outcome on the set analysis that had been planned. And although there was a numerically higher response in the secukinumab group, it didn't reach statistical significance. Unsurprisingly, there was superiority on skin outcomes and some of the other outcome measures.

So I think firstly, it should be noted this is a really brave study. It's the first time somebody has tried to go head to head against a TNF inhibitor, against the market leader, adalimumab, to look for superior efficacy, specifically in the musculoskeletal compartment of the disease. And although it didn't win, it certainly showed non-inferiority over the adalilmumab, as well as superiority in some of the other elements of disease, like the skin.

So I think this helps us to understand where IL-17 inhibitors fit, potentially in the pathway of treatment for psoriatic arthritis. We've known before that they're superior for skin. But I think some rheumatologists have had a concern that they're more a dermatology drug. They're particularly good for skin, but maybe not as good for the joints as a TNF inhibitor would be, and I think this study really puts that notion aside. So it's clear that the drug was at least as good as adalimumab-- numerically, even slightly higher response rates. So I think it really shows that this is a good drug for the musculoskeletal side of things as well as the known superiority in skin.

So obviously, a trial like this will always have some limitations. We're recruiting patients who have predominantly polyarticular disease, and that's not all of the patients that we see in practice. So it's not necessarily generalizable to everybody.

They used a higher dose of secukinumab, a 300 milligram dose, and that's not routinely available to us, unless patients have bad skin, as a first-line biologic. So it's not necessarily the dose that we would always use in practice. But I think it starts to give us some information.

The other thing that we need to think about is, obviously, this was for biologic naive patients going straight onto their first biologic drug. But we see more and more patients who are failing drugs. So thinking about what order we use these drugs in and when, if somebody fails, for example, a TNF inhibitor first, what should we switch to? Those are quite useful follow-on questions that we need to be thinking about when we're selecting biologics.