When and How to Switch Psoriasis Patients from Anti-TNF Therapy Learn how to recognize treatment failure and how to involve the patient in developing a new management strategy. By Jimmy Krell, MD soriasis treatment options have broadened over interfere with TNF receptor interaction, eliminating the the last decade to include some of the most rev- inflammatory and immune responses involved in generating olutionary treatments ever developed for this symptoms of psoriasis (Adalimumab/Humira, Abbott; P condition: biologics. Biologic agents developed Etanercept/Enrel, Amgen and Wyeth; Infliximab/Remicade, for the treatment of psoriasis can be classified by Centocor). their mechanisms of action. T-cell modulating agents interact Both types of treatments have provided psoriasis patients with T cells, key mediators in the immunopathogenesis of the ability to manage their disease and maintain an improved psoriasis (Alefacept/Amevive, Astellas; Efalizumab/Raptiva, quality of life. Anti-TNF agents are the most commonly used Genentech). Anti–tumor necrosis factor (anti-TNF) agents biologic agents in the United States for moderate to severe 42 Practical Dermatology July 2007 psoriasis. Unfortunately, nearly 25 percent of patients treated image, and quality of life, thus eclipsing any benefit seen on with anti-TNF agents experience treatment failure. the rest of their body. Determining which psoriasis patients will respond or are Consider the case of a 34-year-old man with a 19-year his- responding poorly to an anti-TNF requires several considera- tory of plaque psoriasis who presented with 10 percent affect- tions. ed BSA with moderately thick, red, scaly plaques on his Primarily, it is most important to base this decision on the trunk, scalp, and extremities. After failing on previous treat- patient’s level of satisfaction with the treatment. If the patient ments, etanercept (50mg, twice weekly along with feels that his/her response is inadequate, that alone may be cyclosporine initially) treatment was initiated. At 12 weeks, reason to seek alternative options. Additionally, some key the patient experienced 50 percent improvement, and after attributes may indicate ahead of time that a patient might six months the patient experienced 75 percent improvement. respond better to one biologic agent rather than to another. At nine months, though, the patient experienced a significant Two such clinical features are obesity and increased involve- flare (to 15 percent BSA) in his psoriasis and expressed a ment of the hands and/or feet. desire to try an alternate therapy. Efalizumab (1mg/kg/wk) Because biologic treatments for psoriasis tend to be as—if was initiated one week after discontinuation of etanercept, not more—efficacious than other systemic and topical agents, and the patient experienced a steady improvement in skin it is extremely useful for healthcare professionals to monitor disease and achieved a 50 percent improvement at 12 weeks. their patients’ responses and consider alternative biologic ther- Psoriasis symptoms were clear by 24 weeks.1 apy as well as non-biologic therapy for their psoriasis patients. Patients who never respond. In addition to patients who relapse, another inadequate responder would be a patient Types of Poor Responders who never receives a response from a treatment. Generally, The various types of patients who respond poorly or who are patients on etanercept (50mg, twice daily) see reasonable “inadequate responders” can be divided into three distinct results in 12 weeks. If after 12 weeks there is no noticeable categories that I will describe in greater detail below: improvement it should be considered a failure. 1. Patients who respond to treatment and then relapse, A 29-year-old female patient illustrates this point. She had 2. Patients who never respond to treatment; and a five-year history of plaque psoriasis and presented with a 15 3. Patients whose psoriatic arthritis symptoms respond but percent BSA with psoriasis on the trunk, scalp, arms, and whose psoriasis symptoms do not. legs, and mild psoriatic arthritis. After initial treatment with methotrexate, the patient was then treated with etanercept Patients who respond and then lose their response. After (50mg/wk) for 12 weeks. After this time, there was still no about 12 to 18 months of treatment, some patients begin to improvement in symptoms and efalizumab treatment lose their initial response. While this relapse can be extensive, (1mg/kg/wk subcutaneously with concomitant fluocinonide with patients experiencing a return of as much as 50 percent cream 0.05% twice daily) was started. Within three months of their psoriasis, it may be less severe, with a patient gaining the patient experienced a decrease in BSA to less than 10 per- back perhaps only 10 percent of their psoriasis. However, cent. After seven months, the patient achieved 0 percent depending upon the location of the relapse, even a 10 percent affected BSA. return can be significant and deemed a failure to the patient Patients whose PsA symptoms respond while their pso- or the doctor. For example, recurrence of psoriasis on the riasis symptoms do not. The third type of inadequate hands or feet can severely affect a patient’s function, self- responder includes patients who achieve success in treating July 2007 Practical Dermatology 43 Switching Biologic Therapies their psoriatic arthritis but continue to experience the symp- enough recurrence that they need to switch or add another toms of psoriasis. While there is some precedent to maintain therapy. Approximately five to 10 percent of the patients I patients on both anti-TNF agents and T-cell modulators treat with etanercept or adalimumab never respond, while simultaneously, this treatment strate- five percent of patients I start on gy has not yet been widely infliximab don’t respond. researched or accepted by the med- Determining ical community. A recent poster Course of Action presentation showed that patients what constitutes Involving the patient in treatment with psoriatic arthritis and psoriasis decisions is crucial to maintaining a can be successfully treated with a a treatment positive physician-patient relation- combination of etanercept (25mg, ship. Based on the nature of the dis- one to two times/wk) and efalizum- ease, I find that patients want to be ab (1mg/kg/wk). In these cases, “failure” can be proactive in their treatment, and combination therapy with efalizum- some may even express a specific ab and etanercept effectively con- tricky, and desire to switch to another class of trolled both skin disease and arthritis drug. It is important that the patient for patients who previously respond- failure rates be given these choices. Very rarely do ed poorly to either treatment alone. I tell a patient which treatment they The complementary yet differing often vary should be using; Instead, I give them mechanisms of action of these two options. Involving the patient in this treatments most likely contributed process allows him or her to share in to the positive results. greatly from the success or failure of the treat- Consider a 53-year-old man with ment, and this participatory model a 13-year history of moderate psori- practice to of treatment tends to increase com- asis who presented with 12 percent pliance. Choice is essential and, affected BSA, with thick plaques on practice. unfortunately, not enough doctors his knees, elbows, dorsal surface of always participate in this kind of dia- his hands, calves, upper back, and logue with their patients. scalp. The patient was also obese and had diabetes and pso- Determining which treatment a patient should be switched riatic arthritis. Previous treatment with etanercept reduced to can be as difficult as determining which treatment to initi- the symptoms of the psoriatic arthritis but had no effect on ate when the patient first starts therapy. Fortunately, switching the symptoms of psoriasis. After receiving an inadequate anti-TNF inadequate responders can be guided by breaking response on etanercept (25mg twice weekly for one year), the responses down into subgroups. As a general rule, it is best efalizumab therapy was initiated at 1mg/kg/wk. After four to switch classes if a psoriasis patient is not responding to their months of treatments, psoriasis improved, and after 20 anti-TNF treatment and they do not have significant psoriatic months of treatment with efalizumab, the psoriasis was com- arthritis. Further insight into subgroups where this course of pletely clear. After four months of treatment, the patient action is not appropriate include: developed severe arthritis, but was successfully treated with Severe psoriatic arthritis. For patients with severe, life- valdecoxib. The patient remains totally clear at three years altering psoriatic arthritis, including such presentations as bad on efalizumab.1 ankle pain or morning sickness, the best course of action is to Treatment Failure Rates. Determining what constitutes switch to a different anti-TNF. The T-cell modulators do not a treatment “failure” can be tricky, and failure rates often vary target nor are they indicated for the treatment of psoriatic greatly from practice to practice. Generally speaking, of arthritis. For this reason alone, it would be important to main- course, the more psoriasis patients treated in a dermatology tain treatment for the psoriatic arthritis in severe cases. practice, the more “failures” that practice will see in terms of Mild psoriatic arthritis. For patients with mild psoriatic whole numbers. A certain percentage of patients do not arthritis, the best course of action is to control the arthritis respond to any drug, and each physician uses his or her own with an over-the-counter or prescription anti-inflammatory formula or pattern to determine approximate failure rates. pain medication and switch to a T-cell modulator, such as Overall, I have found that about 20 to 25 percent of patients efalizumab. Alternatively, a different anti-TNF agent could who were on etanercept, after about a year, start to have be tried.