Biologic Switching in the Treat-to-Target Paradigm of Plaque Psoriasis
With many different highly effective therapies now available, clinicians and their patients with plaque psoriasis can aim high in achieving their skin clearance goals. The need to switch therapies arises from a number of different factors.
How do you approach the switching of biologic therapies in patients with plaque psoriasis?
Professor of Dermatology, Pathology, and Social Sciences & Health Policy
“For a patient who had not been doing well on a certain biologic right from the start of treatment (ie, they never really had a good response), I will recommend switching them to an entirely different class."
When patients are not doing well on their biologic therapy, they generally have numerous other options because there are so many treatments currently available. If they had been doing well on a particular agent for a significant period of time and now it has stopped working (ie, secondary treatment failure), I will switch them to another therapy in the same class because I know that, for this particular patient, that class has been very safe and effective. If they had not been doing well on a certain biologic right from the start of treatment (ie, they never really had a good response), then I will recommend switching them to an entirely different class.
When switching therapies, I do not recommend any type of wash-out period. My rationale is that if the first biologic had been working, then we would not have needed to switch. The fact that it is not working likely means that it is not having any significant biological effect, and therefore it is probably fine to have some overlap of the new agent with whatever amount of the old agent is left in the body. Further, even if the patient has failed treatment on a first biologic for some reason other than the development of antidrug antibodies, there is likely minimal to no risk with regard to having a short period of overlap between 2 of the biologics used for psoriasis.
James J. Leyden, M.D. Endowed Professor in Clinical Investigation
“Another thing to keep in mind is that pharmacokinetics may be a factor in loss of treatment response.”
We know that there are certain factors that are predictive of a loss of response or not being able to remain on therapy long-term, but we do not really know the extent to which these factors are causal or biologically important. For example, female patients tend to be less persistent on biologics than male patients, and those who are obese tend to be less persistent on biologics than those who are not obese. This could be biological or it could be due to another phenomenon (eg, women wanting to switch before a man would). We are not certain, although I personally believe that there is biology involved. For instance, we know that women may be more prone to autoimmunity than men, so perhaps women are more likely to produce antidrug antibodies than men. And, certainly, patients who are heavier have a higher inflammatory disease burden, and perhaps that is what is driving their lack of persistence.
I agree with Dr Feldman in that the data do seem to suggest that if a patient has secondary treatment failure, meaning that they did well and then lost their response, then there is a significant likelihood of having good results by switching the patient to another biologic in the same class, similar to what they began with. On the other hand, if a patient has a primary treatment failure (eg, they initiated a tumor necrosis factor inhibitor but had an inadequate response), then you would probably want to switch classes.
Another thing to keep in mind is that pharmacokinetics may be a factor in loss of treatment response. For example, say the patient is taking secukinumab once per week for 5 weeks and then proceeds to monthly maintenance dosing and loses response at 6 months. Well, secukinumab has a fairly long half-life, and 6 months in is when you might see a nadir, having proceeded to maintenance dosing. And so, what may be happening for some patients is not truly a loss of response, but rather a need for a higher dosing frequency or a higher dose to recapture their response. In my practice, findings that are suggestive of this phenomenon have occurred in those who have really tough disease, who are often obese. If this is not recognized, clinicians might go from biologic to biologic, trying to stay within the induction period.
Clinical Professor and Medical Director
“I recommend switching therapies when my patient is not happy, and sometimes the decision to switch is not based purely on what I think.”
The patient’s role in the decision to switch therapies is significant. I recommend switching therapies when my patient is not happy, and sometimes the decision to switch is not based purely on what I think. I do enter in my chart their percentage of body surface area affected by psoriasis and their patient global assessment, but those numbers are not typically part of the discussion that I have with the patient.
From the outset, when I first put a patient on a treatment, I will usually tell them that we should aim high for skin clearance. If they have psoriatic arthritis, I will often say that we should aim to treat them so that their arthritis does not affect their daily tasks of living and so that they can forget all about their joint issues. These are my goals, and I state this up front.
Then, with respect to therapeutic switching, the role of the insurance companies and their switching protocols need to be taken into consideration as well. Additionally, when patients hit Medicare age, unless they have a supplemental drug plan, their covered treatment options become more limited. Many of these individuals lose their ability to pay for these biologics. The other consideration, of course, is when the patient loses insurance altogether. Thus, some of these switches are actually not determined by either the patient or the doctor but by the payer. And these challenges are not rare in practice.
Armstrong AW, Koning JW, Rowse S, Tan H, Mamolo C, Kaur M. Initiation, switching, and cessation of psoriasis treatments among patients with moderate to severe psoriasis in the United States. Clin Drug Investig. 2017;37(5):493-501. doi:10.1007/s40261-017-0508-1
Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017;76(2):290-298. doi:10.1016/j.jaad.2016.10.017
Hu Y, Chen Z, Gong Y, Shi Y. A review of switching biologic agents in the treatment of moderate-to-severe plaque psoriasis. Clin Drug Investig. 2018;38(3):191-199. doi:10.1007/s40261-017-0603-3
Mahil SK, Wilson N, Dand N, et al; BADBIR Study Group and the PSORT Consortium. Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR). Br J Dermatol. 2020;182(5):1158-1166. doi:10.1111/bjd.18333
Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072. doi:10.1016/j.jaad.2018.11.057
Özkur E, Kıvanç Altunay İ, Oğuz Topal İ, et al. Switching biologics in the treatment of psoriasis: a multicenter experience. Dermatology. 2021;237(1):22-30. doi:10.1159/000504839
Tsai Y-C, Tsai T-F. Switching biologics in psoriasis – practical guidance and evidence to support. Expert Rev Clin Pharmacol. 2020;13(5):493-503. doi:10.1080/17512433.2020.1767590