For the 17th year, the annual 2020 Winter Clinical Dermatology Conference brought clinicians to Hawaii for an immersive multiday learning experience on medical, surgical, and cosmetic dermatology. From January 17 to January 22, attendees gleaned tips from experts in hot topics in dermatology, mingled with industry professionals in exhibits and at industry expert sessions, and enjoyed networking events with peers Other highlights include:
JAK Inhibitors: An Innovation in Treatment
Seemal R. Desai, MD, discussed the latest breakthroughs in janus kinase (JAK) inhibitors and described the potential therapeutic effects of each product.1
The therapeutic pathway of JAK inhibitors seeks to stop inflammation before it starts. “When you have your cytokine mediator, for example IL-6 or IL-31 in atopic dermatitis or it’s IL-1 alpha or IL-3 in vitiligo, whatever your cytokine is ends up binding to that cellular receptor,” explained Dr Desai. “That subsequently is what turns on that phosphorylation in bringing these two JAK molecules together, which releases the safety signals. Ultimately, when the cytokine binds, bringing these JAK molecules together, that subsequently turns on the recruitment of [signal transducer and activator of transcription proteins], which go into the nucleus and turn on the inflammatory cascade.” JAK inhibitors, however, bind to the kinase domain of JAK to prevent additional inflammation.
The current players include tofacitinib (Xeljanz), indicated for rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ulcerative colitis; ruxolitinib (Jakafi), approved for polycythemia vera and myelofibrosis; and upadacitinib (Rinvoq), which can be used to treat RA. There are several other JAK inhibitors under study:
- Oclacitinib (approved for veterinary use for atopic dermatitis [AD] in dogs);
- BMS-986165 (being studied in phase 2 trials for the treatment of psoriasis and PsA);
- Abrocitinib (phase 3 study on AD just completed);
- Baricitinib (Olumiant; approved in Europe for RA);
- Fedratinib (Inrebic; approved for myelofibrosis);
- Momelotinib (FDA fast-track designation for myelofibrosis); and
- Decernotinib (in phase 2/3 studies for the treatment of RA).
Dr Desai noted that knowing which JAKs are being inhibited by a drug is incredibly important to understanding the safety profile of the drug. “For example, we typically end up seeing more systemic lab abnormalities and issues with blood counts with ruxolitinib than with tofacitinib, and that’s because ruxolitinib blocks JAK2 whereas tofacitinib does not,” said Dr Desai. He suggested performing a blood count, lipid panel, and comprehensive metabolic panel to monitor the patient’s response to a JAK inhibitor. “Generally, if you monitor monthly for the first one to three months, and you don’t see any abnormalities and you’ve kept [the patient] on the same dose, the data is pretty good and you’re likely not to see a major drop in white blood cell count.”
Alopecia areata also can be treated with JAK inhibitors. Dr Desai recommended using topical tofacitinib 2%. Some recent studies, he continued, have shown patients getting on a JAK inhibitor therapy sooner may help with downregulation of transforming growth factor beta and possibly reduce scarring of the hair follicles.
In vitiligo, a lower dose of tofacitinib can be successful. Ruxolitinib cream 1.5% is also effective, but it can cause some adverse events.
Psoriasis has also been studied as a possible target for JAK inhibitor therapy. Most notably, BMS-986165 has been shown to reduce the pathologic hallmarks of psoriasis.
The Rise and Return of Infectious Diseases
Theodore Rosen, MD, reminded attendees to be mindful of infectious diseases in their practice.2 As Dr Rosen noted, a number of infections, from sexually transmitted diseases (STDs) to insect-borne diseases, are on the rise at local, national, and global levels.
The session first detailed the resurgence of STDs. For the fifth straight year, the number of STDs has increased in the United States, including a 19% increase in chlamydia, 63% increase in gonorrhea, and 71% increase in syphilis between 2014 and 2018. European countries, such as Iceland, Ireland, the United Kingdom, and Germany, have seen significant increases in syphilis from 2007 to 2017 (876%, 224%, 153%, and 144% increases, respectively).
These stark numbers may be due to the ease of online “hook-up culture” (as Dr Rosen noted, “We can go online and get a sex partner faster than getting a pizza delivered”). However, data from two studies published in JAMA and Sexually Transmitted Diseases found that persons who participate in online dating tend to be better informed through reading crowd-sourced information on STDs and were tested more frequently for STDs.
Viral STDs are still relevant to the dermatologist. For external genital warts, there is no best treatment. “Three papers, looking at meta-analysis of all the common treatments for external genital warts, intended to show the best treatment. They came to different conclusions using the same data,” said Dr Rosen. Considering these three papers along with guidelines released by the European Union, Dr Rosen suggested using a destructive therapy (eg, cryosurgery, carbon dioxide [CO₂] laser ablation) followed by a secondary therapy a week to two weeks later.