It’s been 11 years since monotherapy and suggest a framework for a number of off-label treatments.
Dr. Alan Menter
The guidelines, issued jointly with the National Psoriasis Foundation (NPF), were published in the Journal of the American Academy of Dermatology.
“I think we are way behind,” Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and cochair of the guideline writing committee, said in an interview. “Most other countries update their guidelines every 1 or 2 years; we were 10 years behind.” The guidelines for systemic nonbiologic drugs follow up psoriasis guidelines issued by the AAD and the NPF on pediatric patients issued earlier this year, and on phototherapy, biologic treatments, and management of comorbidities issued last year.
“A lot has happened in the last 10 years,” said cochair Craig Elmets, MD, professor of dermatology at the University of Alabama at Birmingham. “While much of the interest is on biologic agents, nonbiologics are still used quite frequently, and the guidelines for their appropriate use have changed. Use of the guidelines provides people in the health profession with the most up to date evidence-based information so they can give their patients the best care.”
Dr. Craig A. Elmets
The guidelines acknowledge that the medications it covers are still widely used, either by themselves or in combination with biologic agents; readily available; easy to use; and, in the case of older therapies, relatively cheap.
Methotrexate has been available since the 1970s. Given as an injection or taken orally, the guidelines recommend supplementation with folic acid to counteract methotrexate’s side effects, particularly GI upset. The guidelines note that folic acid is less expensive than folinic acid. Combination therapy with methotrexate and tumor necrosis factor (TNF) inhibitors is more effective than methotrexate monotherapy, with a similar side effect profile, the guidelines state.
Methotrexate is more widely used outside the United States, “but it is a very good, quick fix and it’s much safer in children and young people than it is in people with cardiovascular disease,” Dr. Menter noted. “It’s still the most commonly used drug worldwide because it’s cheap, and you do have to worry about the long-term toxicity which is related the liver issues.”
The guidelines say that subcutaneous administration of methotrexate “may be particularly useful” for patients on higher doses, which when taken orally, are associated with a higher risk of GI effects.
Dr. Menter referred to a 2017 study, which reported 41% of patients treated with subcutaneous methotrexate once a week achieved a Psoriasis Area and Severity Index 75 score of 41% after a year of treatment, compared with 10% of those on placebo (Lancet. 2017 Feb 4;389[10068]:528-37).
The guidelines rate strength of recommendation as class A for methotrexate for moderate to severe psoriasis in adults, recommend supplementation with folic or folinic acid to counteract GI complications and liver problems, and note that adalimumab and infliximab are more effective than methotrexate for cutaneous psoriasis. Class B recommendations for methotrexate and psoriasis include statements that patients should begin with a test dose, especially if they have impaired kidney function; methotrexate is effective for peripheral, but not axial, psoriatic arthritis (PsA); and TNF inhibitors are more effective than methotrexate for PsA.
Approved by the FDA in 2014 for psoriasis, apremilast, which inhibits phosphodiesterase-4, is the newest drug in the recommendations. The guidelines recommend its use for moderate to severe psoriasis in adults, with a class A recommendation. Patients should start on a low dose and then build up to the 30-mg, twice-daily dose over 6 days and should be counseled about the risk of depression before starting treatment. Routine laboratory testing can be considered on an individual basis.
The guidelines also lay out three recommendations (and strength of recommendation) for cyclosporine, a drug that’s been around since the 1990s: for severe, recalcitrant cases (class A); for erythrodermic, general pustular, and palmoplantar psoriasis (class B); and as short-term therapy for psoriasis flare in patients already on another drug (class C).
Acitretin is another longstanding therapy used mostly for palmar-plantar psoriasis, but it can also be used as monotherapy for plaque psoriasis as well as erythrodermic and pustular disease. It can also be used in combination with psoralens with UVA for psoriasis and combined with broadband UVB phototherapy for plaque psoriasis. The acitretin recommendations are class B.
The oral Janus kinase (JAK) inhibitor tofacitinib isn’t specifically approved for psoriasis, but it is approved for RA, PsA, and ulcerative colitis. The drug targets the JAK-STAT signaling pathway that causes inflammation. The guidelines state that tofacitinib can be considered for moderate to severe psoriasis, but lists no strength of recommendation. The recommended dose is either 5 or 10 mg orally twice a day, with a caveat that the higher dose carries a higher risk of adverse events. Patients should be evaluated for getting a zoster vaccine before they begin therapy.
“We thought that, because there was probably a small chance that it might get approved for psoriasis, that we would discuss it briefly,” Dr. Menter said of tofacitinib.
Another off-label use the guidelines address is for fumaric and acid esters, also known as fumarates, which are used to in Europe to treat moderate to severe psoriasis. Dimethyl fumarate is approved for relapsing forms of multiple sclerosis in the United States. The guidelines state that fumarates can be used for psoriasis, but offer no strength of recommendation. Side effects include gastrointestinal disturbance and flushing.
Other treatments that are also addressed in the guidelines include a host of systemic immunosuppressants and antimetabolites: azathioprine, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus, none of which are FDA approved for psoriasis. They’re rarely used for psoriasis, but may have value in selected cases, the guidelines state.
Dr. Menter said that apremilast is the only oral drug in the guidelines, but they are the wave of the future for treating psoriasis. “I think there’s a tremendous potential for new oral drugs – TK2 [thymidine kinase], the JAK inhibitors, and other drugs coming down the pipelines. The majority of patients, if you ask them their preference, would like to take an oral drug rather than an injectable drug. And it would be much easier for dermatologists, they wouldn’t have to train patients on how to do the injections.”
Dr. Menter and Dr. Elmets disclosed financial relationships with numerous pharmaceutical companies. Other authors/work group members also had disclosures related to pharmaceutical manufacturers, and several had no disclosures.
SOURCE: Menter A et al. J Am Acad Dermatol. 2020 Feb 28. doi: 10.1016/j.jaad.2020.02.044.