Head-to-Head Studies in Rheumatic Diseases
Sergio Schwartzman, MD: I had mentioned before that we now have a bounty of richness in terms of the therapies that we have available to manage patients with rheumatic diseases. In terms of trying to differentiate between these, up until recently we did not have many head-to-head studies. Head-to-head studies are now becoming available to us, and they do have different designs. For example, the ORAL Strategy study was a study that compared the Janus kinase 1/3 inhibitor to that same Janus kinase 1/3 inhibitor plus methotrexate to an anti-TNF [tumor necrosis factor] agent with methotrexate. In that study, they designed it as a noninferiority study. What was found was that the Janus kinase 1/3 inhibitor was noninferior to the standard of care, the anti-TNF agent plus methotrexate.
Our studies have become a bit more aggressive. In the SELECT-COMPARE study that was more recently published, this was set up as a superiority study and again comparing a Janus kinase inhibitor, here Janus kinase 1 inhibitor plus methotrexate to an anti-TNF agent plus methotrexate. It was impressive that statistically, it was significantly superior to the standard of care. So those are 2 examples in rheumatoid arthritis.
We’re also beginning to see head-to-head studies in psoriatic disease. With regard to these, it’s an evolving story because outcome measures are still not as clear-cut as they are in rheumatoid arthritis. For example, we look at ACR [American College of Rheumatology criteria] responses in patients with psoriatic arthritis. Whereas that’s not a tool that you would ever use in the clinical management of patients with psoriatic disease, it’s something that the FDA mandates.
There is indeed a study, SPIRIT-H2H, looking at an anti—IL-17 [interleukin 17] therapy compared with an anti-TNF therapy, both with methotrexate. It had an interesting endpoint that is somewhat novel. It had both a skin, meaning a psoriasis endpoint, which was a PASI [Psoriasis Area and Severity Index] 100, and it had an ACR response, which was the ACR50. In that study, if you combine those 2 outcome measures, statistically, there was significant superiority for the IL-17 therapy. We could argue about the validity of that outcome measure because it really hasn’t been tested prior to this study. Nonetheless, here we are looking at a head-to-head study comparing standard of care, an anti-TNF agent plus methotrexate, to a completely new class, which is an IL-17–driven therapy.
I think we’re talking about really different classes. If we are to focus on safety, I do think that’s a very important element with regard to choosing therapies. This is because you have to apply it to a specific patient. If, for example, I have a patient who has had recurrent serious infections, who has diabetes, and is on low doses of steroids, I’m going to try to use a therapy that does not have serious adverse events as 1 of its boxed warnings. As an example of that, if we look at the anti-TNF class versus the anti-IL-17 class, the IL-17 class does not have a boxed warning for serious infections.
In terms of safety, in that type of circumstance, I would choose an IL-17—driven therapy. However, if we’re still to focus on safety, I’m going to give you the opposite example where I would choose an anti-TNF over an IL-17. One of the safety concerns in patients who are treated with IL-17s is that they can develop inflammatory bowel disease. The data for that are evolving, but I think it’s accepted that in some patients that is a risk that occurs. So if I have a patient who has had a history of inflammatory bowel disease and needs a biologic agent and I’m making a safety-driven decision, I am not going to use the IL-17 class. I am going to use the anti-TNF class because here I would be killing 2 birds with 1 stone. Most of the anti-TNFs, not all of them, actually do treat inflammatory bowel disease.
Before deciding on treatment, in terms of the safety components across all of the classes, you do have to take that into account depending on the specific variables applicable to a given patient. But if we were to go to the targeted synthetics as another example where safety would drive a decision, if I’m deciding between an anti-TNF agent and a targeted synthetic—1 of the JAK inhibitors—in a patient who has rheumatoid arthritis and who happens to have multiple sclerosis as well, there’s no way that I would use an anti-TNF agent. This is because in that type of circumstance, I know that I could make the multiple sclerosis worse, whereas the JAK inhibitors, as another example, do not. They don’t treat it, but they don’t make it worse.
Knowing the nuances of the individual therapies that we’re using and differentiating them, not only in terms of efficacy but as the question was posed importantly in terms of safety, is an important determinant of which therapy you’re going to use in a given patient.
Transcript edited for clarity.
