2020 AAD Psoriasis Guidelines: Methotrexate Gets a Makeover

Methotrexate is an old friend of dermatologists that we know well.

We use it primarily for psoriasis, but it is also used for myriad skin conditions, ranging from common (atopic dermatitis) to rare conditions such as autoimmune connective tissue or blistering disease (often as a steroid-sparing agent) to unusual forms of cutaneous T-cell lymphoma. For its 2020 makeover, imagine a glossy television commercial, complete with a celebrity endorsement, invoking its selling points:

1. It is so convenient, just once-a-week dosing in a simple pill that can be dosed to your specific needs!

2. Forty-five percent of patients achieve at least a 75% improvement in their skin!

3. And you are not going to believe this, the celebrity gushes: It only costs about $15 a month — no prescription insurance required! That’s right, 15 bucks per month — compare that with other options that can cost thousands of dollars a month!

4. More than 50 years of experience! Millions treated!

And now for the disclaimer: Regular tests recommended to monitor your blood count and liver function, let your doctor know if you have kidney problems, do not drink alcohol or do so only in moderation, do not become pregnant or get someone pregnant while taking it, tell your doctor about all medications and supplements you are taking as drug interactions can be serious, and patients may experience nausea, vomiting, mouth sores and hair loss, with rare reports of lymphoma and lung inflammation.

Now, a lot of patients are willing to accept these risks and inconveniences. But then comes the last warning: Liver biopsy. Our 2009 American Academy of Dermatology guidelines recommend liver biopsy as early and often as after 2 to 6 months of treatment and then after every 1 g to 1.5 g of methotrexate in patients who had risk factors for liver disease such as diabetes, obesity or hyperlipidemia. The liver biopsy was, and still is, dreaded by prescribers and, of course, even more so by our patients. And this is where methotrexate gets a major makeover in 2020. Thanks to dramatic advances in noninvasive blood and imaging tests, most patients will not need a biopsy at any point in their treatment.

Serologic tests include fibrosis-4, an algorithm based on liver enzymes, platelet count and age (available online), and other patented tests such as FibroTest/FibroSure (BioPredictive), FibroMeter (Echosens) and Hepascore (Quest Diagnostics). Note that some of the patented tests require the patient to be fasting overnight. Imaging approaches include FibroScan (Echosens), a vibration-controlled transient elastography and the most used to assess liver fibrosis. Magnetic resonance elastography is a more accurate technique that should be considered if there is a technical failure with vibration-controlled transient elastography or in patients with a particularly high risk for failure such as BMI of 40 kg/m² or greater.

Similar to 2009 guidelines, there is stratification based on patient risk factors for liver disease. The guidelines recommend noninvasive blood serology at baseline for all patients. If there are no risk factors for hepatotoxicity and the baseline serology is normal, then you repeat this annually. If the annual blood serology becomes abnormal or if the patient has received a cumulative dose of 3.5 g to 4 g of methotrexate, then noninvasive imaging is recommended. For most of us, the imaging tests would be done in collaboration with a gastroenterologist. If there are risk factors for hepatotoxicity, then noninvasive imaging is recommended annually.

So, methotrexate, our old friend, looks better than ever with the 2020 AAD guidelines, which welcome blood serology and noninvasive imaging as a modern twist on this old drug, making it easier to prescribe and manage for our patients. Say goodbye to the old recommendations for liver biopsies and hello to progress.

References:

Holliday AC, Moody MN, Berlingeri-Ramos A. Skin Therapy Lett. 2013; Mar-Apr;18(3):4-9.

West J, Ogston S, Foerster J. PLoS One. 2016;doi:10.1371/journal.pone.0153740.

Menter A, et al. J Am Acad Dermatol. 2009;doi:10.1016/j.jaad.2009.03.027.

Menter A, et al. J Am Acad Dermatol. 2020;doi:10.1016/j.jaad.2020.02.044.