Jose Scher, MD, on Combination Therapy in Psoriatic Arthritis
– The case for reconsidering the one-medication-at-a-time paradigm for a multi-domain disease
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The time has come for combination therapy in psoriatic arthritis (PsA) care.
That was the message from three PsA experts in a commentary published recently in .
In particular, the commentary argued that "PsA remission can best be achieved when diverse pathobiological pathways are targeted with a combination approach comprised of agents with distinct, but synergistic, mechanisms of action that counter inflammatory events in all affected domains."
Jose Scher, MD, director of the New York University Langone Psoriatic Arthritis Center, served as a co-author of the commentary. Scher recently discussed his commentary with 鶹ý. The exchange has been edited for length and clarity.
What led you to write this commentary?
Scher: When we talk about treating PsA, once there are musculoskeletal manifestations we can use medication to address one pathway -- say with a TNF or an IL-17. But in actuality there are so many pathways with PsA that we very well may need multiple therapies. So the current paradigm may need to be reconsidered because we're only using one medication at a time.
How would you describe the current paradigm when it comes to PsA therapies?
Scher: We know from the data that tissues that are affected in PsA are not necessarily affected by one type of cell or cytokine. Rather, we are looking at what we consider a multi-domain disease.
For example, if you compare PsA with rheumatoid arthritis (RA), in RA it's only the joints that are affected, or perhaps it's cardiovascular, or what have you. But in PsA you have at least two domains. Treating one domain at a time, one type of cell, or one pathway at a time will not necessarily help achieve better control, much less remission.
The combination approach has been shown to work in oncology, for example. Initially the treatment of certain cancers was with one medication, and it wasn't until the combination therapy that we began to see better outcomes and higher remission rates.
What, if anything, should clinicians be aware of when it comes to PsA combination therapies?
Scher: Obviously, combination approaches are not approved by the FDA, so there's nothing we could do that would be covered by insurance. So we need to fundamentally prove that our hypothesis is right so that it's known scientifically if a particular combination works in a clinical trial. A lot of the new medications for psoriatic disease are not immunosuppressive, and therefore the concern for safety can be mitigated in such combination trials.
In the meantime, are there any actions clinicians can take right now in this area?
Scher: The first piece of advice would be to simply start thinking about it. Second, maybe a clinician could obtain some sort of green light from an insurance provider to try different drugs in certain combinations. Or if they have somebody taking one medication without significant improvement, they may want to try another medication without combining per se; it's just that you're not washing out that initial medication. It can be a little proof of principle that a certain combination works.
I would add that if you have some observational data from a couple of cases where combination therapy has been done one way or another in people with PsA and you think it would be helpful for other clinicians to know about them, those data can be published. But the larger trials will take several years.
Read the study here and expert commentary on the clinical implications here.
Scher reported financial support from UCB, Janssen, Abbvie, Pfizer, BMS, Lilly, Novartis, and Sanofi.
Primary Source
Arthritis & Rheumatology
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