key: cord-0839597-1lpl26eo
authors: Peterson, Danielle; Damsky, William; King, Brett
title: The use of Janus kinase inhibitors in the time of SARS-CoV-2
date: 2020-04-09
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.03.099
sha: ad5dd2193095b5ede55e2968d10c5c2541a5ccf7
doc_id: 839597
cord_uid: 1lpl26eo

nan

During the time of the SARS-CoV-2 pandemic, questions arise regarding patients being treated with 37 immunomodulatory therapies. In particular, is there an increased risk of acquiring the infection or 38 experiencing a worse outcome from SARS-CoV-2? While this exact question is presently unanswerable, 39

we can look at safety data from clinical trials to try to understand patient susceptibility to different 40 infections. While others have addressed this in the context of biologic 1 or classical small molecule 41 therapy 2 , the risk of Janus kinase inhibitor (JAKi) treatment has not been addressed. In light of the 42 growing off-label use of JAKi in dermatology in addition to pharmaceutical industry sponsored clinical 43 trials of JAKi for alopecia areata, atopic dermatitis, vitiligo, etc, dermatologists need data to better 44 understand the risks of JAKi treatment in order to best manage and counsel our patients during this 45 unique time. 46

We analyzed and collated Adverse Events data from JAKi clinical trials. In particular, we focused on 48 infections and pulmonary toxicities observed across the different FDA-approved JAKi for their FDA-49 approved indications. When available, data from phase II or III clinical trials for dermatological 50 indications was included. Table 1 shows the rates of various infections, including upper respiratory 51 infections, nasopharyngitis and influenza, for JAKi-treated groups versus placebo groups. Overall, rates 52 of infectious events are only mildly increased in JAKi-treated patients. We also collated pulmonary 53 toxicities of JAKi to identify potential risks of worsening severe respiratory disease from SARS-CoV-2, and 54 such toxicities are all but absent. 55 56 In order to understand the infection data, it is helpful to understand the mechanism and 57 pharmacokinetics of JAKi. Cytokines can drive autoimmunity when their activity is exaggerated ( Figure 3 1A). JAKi, which are taken orally 1-2 times per day, largely impact pathogenically elevated cytokine 59 activity, with relative sparing of normal cytokine activity because drug concentrations are sub-60 therapeutic for part of the day ( Figure 1B In this time of the SARS-CoV-2 pandemic, we must be as informed as possible regarding the risks of the 75 treatments we prescribe our patients. Of course, shared decision-making reigns supreme, but without 76 data we, as physicians, will be unable to provide our patients the guidance they rely on us for. 

Should biologics for psoriasis be interrupted in the era of

Inflammatory Diseases

liver abscess (1), pleural effusion (1), pyelonephritis (1) 117 2. 10 mg dose-anal abscess (1), cellulitis (1), febrile infection (1), otitis externa (1), pneumonia (1) 118 3. 10 mg dose -furuncle (1) 119 4. 1mg dose -peri-tonsillitis

PNA (8), 122 sinusitis (1), sepsis (1), lower respiratory infection (1) 123 7. 15mg dose-viral infection (1)