Physicians refine psoriasis treatment strategies using biologic agents

Miami Beach, Fla. - As the use of therapy for moderate-to-severe psoriasis grows, an expert says, physicians continue refining treatment strategies.

“Biological therapies have been a major advance in psoriasis treatment,” says Robert E. Kalb, M.D., clinical professor of dermatology, State University of New York, Buffalo, School of Medicine. Patients who have severe psoriasis and fail conventional therapies can choose from this new armamentarium, he says, using regimens that increasingly match drug attributes with individual patient characteristics.

If the efficacy of a tumor necrosis factor (TNF) blocker starts waning, which suggests autoantibodies to the drug, dermatologists should consider switching TNF agents, says Dr. Kalb, who spoke at the 71^st annual American Academy of Dermatology meeting. “The autoantibodies will not affect the second agent.” Another option, he says, is increasing the patient’s dose or dosing frequency if feasible.

Some experts recommend adding methotrexate when a biologic’s efficacy begins to wane. In this regard, “There’s no right or wrong answer. Others have argued that you should always consider using methotrexate with a biologic drug to prevent autoantibodies.”

A recent study in patients with psoriasis shows for the first time that such a combination works better than etanercept alone (Gottlieb AB, Langley RG, Strober BE, et al. Br J Dermatol. 2012;167(3):649-657.).

Conversely, Dr. Kalb says, if a patient fails to respond to an initial TNF therapy, data suggest switching to a drug with a different mechanism, such as the interleukin (IL)-12/IL-23 blocker ustekinumab. A recent five-year ustekinumab study showed no significant safety issues, including cancer or major adverse cardiovascular events (Papp KA, Griffiths CE, Gordon K, et al. Br J Dermatol. 2013 Jan 10. [Epub ahead of print]).

Presently, Dr. Kalb adds, three IL-17 blockers (brodalumab, Amgen; secukinumab, Genzyme; ixekizumab, Eli Lilly) are in phase 2/3 clinical trials. Among small-molecule drugs, he says, “Tofacitinib (Pfizer), a Janus activated kinase (JAK ) inhibitor, was recently approved in rheumatoid arthritis.” Also, the phosphodiesterase 4 inhibitor apremilast (Celgene) recently completed phase 3 trials for psoriasis and psoriatic arthritis.

More conventional options

For phototherapy, he says, narrowband 311 nm UVB (NBUVB) represents the gold standard. Combining it with low-dose acitretin rivals the efficacy of biologics, Dr. Kalb adds. The mechanism of action of phototherapy is still not entirely clear, but recent data suggest NBUVB suppresses the IL-23/IL-17 axis (Johnson-Huang LM, Suárez-Fariñas M, Sullivan-Whalen M, et al. J Invest Dermatol. 2010;130(11):2654-2663).

“Additionally, low-dose acitretin has far fewer side effects than we’ve been led to believe” by labeled data based on high-dose acitretin monotherapy. Furthermore, he says, patients who respond well to NBUVB plus acitretin often can decrease or eliminate one of the treatments over time.

“Don’t forget about home phototherapy units,” Dr. Kalb says. In a randomized NBUVB trial, in-office treatments and home-based treatments showed similar results and costs, although patients preferred the home unit (Koek MB, Sigurdsson V, van Weelden H, et al. BMJ. 2010;340:c1490). “If a person is responding well and would consider a home device, it requires effort on the physician to obtain the necessary insurance authorization.”

Methotrexate and cyclosporine

As for methotrexate, Dr. Kalb says, five recent placebo-controlled studies show that it typically achieves psoriasis area severity index (PASI) 75 results in 40 percent of patients. Efficacy becomes apparent in 12 to 16 weeks, he says.

“If there is not an adequate response, then a biologic agent can be added while continuing methotrexate (to improve efficacy and prevent autoantibodies),” Dr. Kalb says.

Folic acid supplementation (1 mg daily) reduces methotrexate’s hepatic, gastrointestinal and hematologic toxicity without compromising efficacy (Prey S, Paul C. Br J Dermatol. 2009;160(3):622-628). Similarly, Dr. Kalb says, patient self-administered subcutaneous methotrexate provides increased efficacy in arthritis and perhaps psoriasis, while improving tolerance.

Moreover, “If you select patients properly, without significant risk factors, the vast majority won’t need serial liver biopsies. It could be argued that methotrexate itself does not cause liver fibrosis without contribution from other risk factors.” Primary risk factors include obesity, diabetes and excess alcohol use, he adds.

Conversely, Dr. Kalb says that hematologic toxicity is the most serious adverse event associated with methotrexate use in psoriasis, and the likelihood of hematologic toxicity increases in patients with decreased creatinine clearance.

“Cyclosporine can provide a quick fix,” often providing initial relief within days to weeks, Dr. Kalb says. He suggests beginning with high doses (4 mg/kg to 5 mg/kg), then lowering the dose if feasible. “Because of the long-term renal toxicity and hypertension, it’s sometimes not practical long-term. But in low doses, it can be combined with other treatments and often is very effective.”

European physicians commonly prescribe cyclosporine for intermittent courses of three to four months, he says. “It’s also used as a bridging agent between therapies,” and to help quell flares.

Disclosures: Dr. Kalb is an investigator, speaker and/or consultant for Abbott, Amgen, Janssen, Leo, GSK/Stiefel. His group practice provides phototherapy and infusion services for psoriasis.