Psoriasis treatment failure can occur when a therapy is not effective right from the beginning for that particular patient (ie, primary failure), or there can be a secondary failure when the drug works well for a while but then stops working, which may be most commonly due to the development of antidrug antibodies. It is also possible for some individuals to experience primary failure due to antidrug antibodies. Further, if a drug works and then stops working, the patient may have developed antidrug antibodies, and switching them to a different treatment in the same class makes sense because antibodies that bind and inactivate one drug are unlikely to bind another. If the drug never really worked well, the disease may be resistant to drugs that have that particular mechanism of action, and you may be more likely to consider switching to an agent in an entirely new class. However, this is not a hard-and-fast rule.

Importantly, poor adherence is relatively common and may look like treatment failure. In a study with adalimumab, we found that adherence was variable and was sometimes quite poor. Adherence to systemic treatments also decreases over time, with an overall adherence rate of 67% for injectable biologic medications. Motivation alone does not make patients very adherent to treatment. Often, those with the worst disease were not taking the drug the way that it was prescribed. 

When assessing adherence, I avoid asking patients directly whether they take their medication as directed, because they may be sensitive or embarrassed to admit that they have not always been taking their medication regularly. So, I ask them indirectly, with questions such as whether they are keeping the extras refrigerated, which makes the dialogue seem like it is more about refrigeration than about adherence. If they say that they keep all the extras in the refrigerator, which is common, then it is likely that they are not taking the medication regularly as directed. If they say that they never have any extras, then they are more likely taking it regularly. 

There are a number of factors that can impact a patient’s adherence and, ultimately, their response to psoriasis treatment. Some patients are afraid of side effects, and they may take their therapy less frequently than directed for that reason. For others, I think that a larger factor is just a natural human tendency to not do things on a rigid schedule unless there is something forcing them to do so. Even people who are very motivated and who should know better are often not 100% perfect in taking their medications, and this is part of being human. In the past, when there were fewer treatment options, I was very concerned when patients would take their tumor necrosis factor inhibitor intermittently because this can lead to greater immunogenicity, antidrug antibodies, and loss of efficacy. Today, we still want patients to take their medications regularly as directed, but now there are more options available if they do not and if that results in loss of efficacy.