Newer therapies to treat psoriasis and psoriatic arthritis are more likely to be successful in patients with no prior exposure to biologics. Traditional therapies remain an option but, unlike newer treatments, require monitoring for toxicities.
SAN FRANCISCO, CA - Factors such as lack of response to previous therapies or the presence of comorbidities should influence the choice of treatment for patients with psoriasis and psoriatic arthritis, according to several leading dermatologists speaking at the 2015 meeting of the American Academy of Dermatology at a course on AAD psoriasis guidelines.
With a drug like apremilast, which is indicated to treat moderate to severe psoriasis and psoriatic arthritis, patients who are biologically naive can expect the greatest chance of response to the drug. However, the potential for response diminishes if patients have previously been exposed to biologic therapy, notes Alice Gottlieb, M.D., Ph.D., Dermatologist-in-Chief, Harvey B. Ansell Professor of Dermatology, Tufts Medical Center and Tufts University School of Medicine, Boston, Mass.
"It is not a drug where you tell patients that they have a high chance of responding," says Dr. Gottlieb.
Similarly, the possibility of response to the anti-IL-12p40 agent ustekinumab will reduce if patients are not naive to TNF blockers.
"Most of our patients with psoriatic arthritis will have first tried TNF-blockers," says Dr. Gottlieb. "You must tell them there is a possibility of a third of a chance of response and that it will take 24 weeks [to see a response]."1,2
Factors in selecting a therapy
In terms of deciding on a therapy to manage psoriasis, the first question that clinicians should pose is if the patient in front of them has arthritis, according to Dr. Gottlieb.
"If they have psoriatic arthritis, you have to treat that," says Dr. Gottlieb, noting that many physicians do not catch the presence of psoriatic arthritis in their patients. "The first line therapy is methotrexate, TNF blockers or methotrexate in combination with TNF blockers."
READ: Psoriasis Guidelines
With newer therapies, it is important to recognize "what we don't know", Dr. Gottlieb says, advising that, since there are no data supporting the use of apremilast in combination with other drugs, clinicians should avoid combining the oral agent with other therapies.
The emergence of IL-17 inhibitors has allowed patients to achieve even greater clearance of their disease with measurement scales like Psoriasis Area Severity Index (PASI) being used. A significant portion of these patients reach PASI 90. There is a correlation between PASI levels and the Dermatology Quality of Life Index, indicating that greater clearance of disease improves quality of life to a greater extent.
"These are patients [reaching PASI 90] whose lives are minimally affected by psoriasis," said Dr. Gottlieb.
Craig Leonardi, M.D., Clinical Professor of Dermatology at St. Louis University Medical School in St. Louis, Mo., echoes Dr. Gottlieb's remarks about the efficacy of IL-17 inhibitors, noting that success as measured by PASI is increasing with successive generations of biologic therapies and that the IL-17 inhibitors are producing even greater clearance of disease than the previous generation of biologic agents.
Secukinumab, for example, which was recently approved for psoriasis, is a "high-performance, skin-clearing" drug with improvements seen as early as three weeks after initiation of treatment, notes Dr. Leonardi. Similarly, ixekizumab is producing improvement in patients as early as one week after treatment has started.
During the conference, Dr. Leonardi addressed concerns about skin cancers and phototherapy use in psoriasis management, explaining that patients who are phototherapy users may be at risk for developing skin cancers, forcing clinicians to look for alternatives to phototherapy.
An added challenge for clinicians is being presented by patients who also have numerous co-morbidities such as hypertension, dyslipidemia, diabetes and obesity. All this information has to be considered in selecting a therapy that is appropriate, says Dr. Leonardi. The selection of methotrexate to treat psoriasis, for example, may pose a problem in the presence of diabetes, as may cyclosporine, notes Dr. Leonardi.
The incidence of major adverse cardiovascular events (MACE) and the use of biologics has been studied, but to date, it is not clear if all the TNF blockers are cardioprotective, says Dr. Leonardi.
"Biologic drugs for the most part are the best choice for patients with complicated medical history and medical problems," Dr. Leonardi says, adding that "they solve the problem of internal organ side effects, and interaction with other medications or treatments."
AAD president Mark Lebwohl, M.D. and Professor and Chairman in Dermatology at Mount Sinai Medical Center in New York, NY, says that clinicians may find that they are continuing to use more traditional therapies like methotrexate in their practices because of the significantly higher costs associated with emerging psoriasis therapies and pressure from insurance carriers to offer less expensive therapies.
If they are prescribing methotrexate, they should consider monitoring the impact of methotrexate on the bone marrow in addition to the liver.
"You should check blood counts one to two weeks after [starting methotrexate], which is when the peak effect of methotrexate on bone marrow [occurs]," cautions Dr. Lebwohl, noting that counts should also be monitored at regular intervals thereafter.
Cyclosporine is another traditional therapy for psoriasis, but the dose of the drug may have to be reduced, or the drug stopped altogether, if there is a decrease in renal function in patients. Another toxicity associated with its use is hypertension.
"You can take care of the patient with psoriasis [on cyclosporine] if you are watching the creatinine and blood pressure," says Dr. Lebwohl.
Dr. Gottlieb is a consultant for Celgene, the maker of apremilast, which provides research/educational grants directly to Tufts Medical Center; for Janssen Biotech, Inc., manufacturer of ustekinumab, which provides research/educational grants directly to Tufts Medical Center; and is a consultant for Amgen Inc., Novartis, and Lilly, all of which provide research/educational grants directly to Tufts Medical Center. Dr. Leonardi is a consultant and speaker for AbbVie and Celgene; and a consultant for Amgen, Dermira, Lilly, Leo Pharma, Sandoz, UCB, and Pfizer. Dr. Leonardi is an investigator for Actavis, AbbVie, Amgen, Celgene, Coherus, Dermira, Lilly, Galderma, Janssen, Merck, Pfizer, Sandoz, Stiefel, Leo Pharma, Novartis, and Wyeth. Dr. Lebwohl has been an investigator for many companies that make psoriasis products but does not personally receive any money from them.
1. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis : 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 Trial. Lancet. 2013;382(9894):780-9.
2. Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomized, double-blind, placebo-controlled, crossover trial. Lancet. 2009;373(9664):633-40.