patient care perspectives

Psoriasis Flare or Diminishing Response to Treatment?

by Steven R. Feldman, MD, PhD

Overview

In patients with psoriasis, a disease flare may result from a loss of response (eg, due to antidrug antibodies), increased disease activity, or adherence issues. Challenges with adherence may extend beyond simply forgetting to take the medication at the right interval.

Expert Commentary

Steven R. Feldman, MD, PhD

Professor of Dermatology, Pathology, and Social Sciences & Health Policy
Wake Forest School of Medicine
Winston-Salem, NC 

“Adherence is a very important issue. Additionally, there is no question that you can have a biologic that is extraordinarily effective for patients with more severe forms of psoriasis and then just completely stops working.”

Steven R. Feldman, MD, PhD

There are forms of psoriasis that are more limited, and then there are the more severe forms of psoriasis. In the case of limited disease, when you treat the patient with a topical therapy that does not work well or it works well initially and then stops working, my experience has been that the number one reason for poor response is nonadherence. We conducted a long-term study following patients taking topical fluocinonide for their psoriasis over the course of 1 year. The use of the medication dropped off very quickly in the first few weeks and remained abysmally low for the rest of the year. I am convinced that when you see treatment failure in patients with limited psoriasis, it is very often due to challenges related to taking the medication. So, adherence is a very important issue.

Additionally, there is no question that you can have a biologic that is extraordinarily effective for patients with more severe forms of psoriasis and then just completely stops working. I do not know of any way clinically to discern whether the patient’s disease suddenly worsened or if they developed an antibody against the drug. We do not typically measure antidrug antibody levels in practice, but I would speculate that the loss of efficacy is often due to antigenicity, and lack of adherence can be an issue that leads to antibody production. The nature of antidrug antibody assays is such that you cannot really compare the antigenicity of different drugs; they are different tests with different cutoffs. However, I think that the new therapeutic antibodies we prescribe may be less antigenic than the earlier ones because, if you look at the early agents (ie, etanercept, adalimumab, infliximab), persistence is not very impressive. Persistence has improved with the newer therapies, but you will still lose perhaps 5% of the patients per year with even the best of drugs and the most stringent follow-up in clinical trials.

Another issue in patients treated with self-injectable medications is that, even if somebody is trying really hard to be compliant, they may not be. For instance, when patients are instructed that medications need to be refrigerated, some may reason that keeping them in the freezer would be better, but, unfortunately, repeated freezing and thawing can denature proteins and lead to loss of efficacy. It is also true that psoriasis can be a very stressful disorder, and, for patients who are under an enormous amount of stress, it may be realistic to expect that they will not take their medications correctly.

References

Alinia H, Moradi Tuchayi S, Smith JA, et al. Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring. Br J Dermatol. 2017;176(3):759-764. doi:10.1111/bjd.15085

Fagerli KM, Kearsley-Fleet L, Watson KD, et al. Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register. RMD Open. 2018;4(1):e000596. doi:10.1136/rmdopen-2017-000596

Kimball AB, Kerbusch T, van Aarle F, et al. Assessment of the effects of immunogenicity on the pharmacokinetics, efficacy and safety of tildrakizumab. Br J Dermatol. 2020;182(1):180-189. doi:10.1111/bjd.17918

Liau MM, Oon HH. Therapeutic drug monitoring of biologics in psoriasis. Biologics. 2019;13:127-132. doi:10.2147/BTT.S188286

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

Menting SP, Coussens E, Pouw MF, et al. Developing a therapeutic range of adalimumab serum concentrations in management of psoriasis: a step toward personalized treatment. JAMA Dermatol. 2015;151(6):616-622. doi:10.1001/jamadermatol.2014.5479

Rousset L, Halioua B. Stress and psoriasis. Int J Dermatol. 2018;57(10):1165-1172. doi:10.1111/ijd.14032

Wilkinson N, Tsakok T, Dand N, et al; BSTOP Study Group; PSORT Consortium. Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study. J Invest Dermatol. 2019;139(1):115-123. doi:10.1016/j.jid.2018.07.028

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