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.