Observation and consideration on using of JAKi in clinical trials in times of COVID-19.

Dear Editor,

JAK inhibitor (JAKi), such as tofacitinib, seems to be a promising drug for the treatment of alopecia areata (AA) with mild adverse effects. The most frequently observed adverse events were upper respiratory infections. During the epidemic of COVID‐19, dose JAKi using increase the risks of infection?

There are different opinions on whether to stop using JAKi during the epidemic. ,

Increased levels of interferons α, β, and IL‐6 in SARS‐CoV‐2 infected patients with severe phases, which primarily mediated by the JAK/STAT pathway. In animal models of SARS and MERS, interferon α and β action were also harmful in later stages. Therefore, some studies suggest that JAK/STAT pathway inhibition might be a potential strategy for the later stage of COVID‐19. Richardson and Napolitano et al., proposed that both baricitinib and upatacitinib should not be stopped during the COVID‐19 pandemic due to their potential treatment. ,

However, the infectious rates (upper respiratory infections, nasopharyngitis, and influenza) are mildly increased in JAKi treated groups compared to placebo. Peterson suggested that discontinuation of JAKi in the initial infection of SARS‐CoV‐2 might be beneficial. While, both opinions are theoretical and more clinical data are needed to support their studies. It is an uncertainty that JAKi using is beneficial or risks for COVID‐19 infection and related disease morbidity. However, this is important for patients who are taking JAKi.

Herein, we report three patients who are administered Jaktinib Hydrochloride (Suzhou Zelgen Biopharmaceuticals Co., Ltd; JAKi) for AA clinical trials during the COVID‐19 pandemic in Hubei province, China. The details of the patients are shown in Table 1. The first patient had universal alopecia for 30 years; she took the JAKi orally for 37 days. There was no visible hair and eyelashes growth during the treatment period nor changes after stopping the medication. Patient 2 had total alopecia for 7 years, and JAKi was taken orally for 40 days. Eyelashes grew partially after 4 weeks and did not fall off till today. Patient 3 had moderate AA for 4 years and took JAKi for 26 days; the hair growth occurred after 3 weeks, and no relapse after stopping the medicine. These three patients are all Hubei residents and enrolled in the clinical trials before COVID‐19 started in China. They took JAKi for 4 to 8 weeks during the epidemic peak until the medicine discontinued around mid‐February because of the city lockdown and travel restrictions. All the three patients and their household were not contracted the COVID‐19 (without any symptoms and with negative test results). We provided our observation here and showed that JAKi using at least no more risks for COVID‐19 infection of the three patients. Notably, our sample size is too small, and need more observations to ascertain benefits or risks for patients and make a better decision.

TABLE 1

The data of the three patients with JAKi administration

Number	Age	Gender	Duration of disease (y)	Duration of treatment (d)	Hair or eyelash growth	relapse after interruption	COVID infection	Causes of interruption
1	36	F	30	37	No	/	No	Medicine discontinued
2	28	F	7	40	Yes	No	No	Medicine discontinued
3	49	F	4	26	Yes	No	No	Medicine discontinued

During the epidemic, the three patients in the study had a strong desire to continue treatments, and two of them showed good clinical efficacy. Therefore, it is hard to decline them. Since the probable prolonged the COVID‐19 pandemic, for patients on study trials, how to complete the study and keep them safe. Here are our considerations.

First, provide safety advice to patients and keep ascertaining the infection and quarantine status of the patients and their household. Second, recommend the household take pictures of patients' hair and eyelash under a fixed background, body position, and angles for getting qualified photos. Remote visits (by telephone, video, and qualify photos) replace visits in person. Necessary laboratory tests can be done at a local hospital, and the study‐related assessments were made by the PI remotely. Third, study medicine can be couriered to patients.

CONFLICT OF INTEREST

The authors declared no potential conflict of interest.