You will no doubt have heard about baricitinib, one of the Janus Kinase (JAK) inhibitor drugs developed by the pharmaceutical company Eli Lilly. However, there are many of these JAK inhibitors, as other pharmaceutical companies produce different versions. The JAK inhibitor drugs work by blocking the action of the Janus Kinase proteins, which limits their ability to send inflammatory signals into the cell. When taken orally, they affect many cells in our body, including hair cells, and for some people with alopecia areata (AA) this results in hair regrowth. In addition, there is some limited evidence that JAK inhibitors may be effective in scarring alopecias (Yang, et al. 2018) and clinical trials are underway in the US to test this further (https://clinicaltrials.gov/study/NCT05076006 & https://clinicaltrials.gov/study/NCT05549934). There are 4 different Janus Kinases: JAK1, JAK2, JAK3 and TYK2. Besides being developed by different companies, the JAK inhibitor drugs are also different in which JAK proteins they interact with: baricitinib, for example affects JAK1 and JAK2, while ritlecitinib primarily affects JAK3.

The results of a new clinical trial for ritlecitinib, a JAK inhibitor developed by Pfizer, have just been published in The Lancet. This new trial with ritlecitinib contained 718 people with severe alopecia areata (>50% scalp hair loss) of 12 years or older. This means it's different from the trial for baricitinib, which only included adults >18 years of age. In the ritlecitinib trial, participants were randomly assigned to receive different doses for 24 weeks: 50mg, 30mg, 10mg or 0mg (placebo) daily. Some also received a ‘loading dose’ of 200mg for the first 4 weeks. A second 24-week period (‘extension period’) followed in which those on ritlecitinib continued on the same dose and those placebo switched to 50mg or 200mg loading dose + 50mg. To avoid bias in the results, neither the investigators nor the patients knew which dose patients were receiving (we call this double-blinding).

The main outcome that was used to determine ‘successful treatment’ was a Severity of Alopecia Tool (SALT) score of 20 or less (i.e., hair regrowth to the point where less than 20% of the scalp was affected). After 24 weeks, 23% of people on the 50mg dose, 14% of people on the 30mg dose, and 2% of people on the 10mg dose achieved regrowth to SALT ≤20. In the placebo group, 2% of people also experienced regrowth to SALT ≤20. In the groups of people that received a 4-week loading dose of 200mg at the start of their treatment, the proportion of people experiencing significant regrowth was higher at 31% in the 50mg group and 22% in the 30mg group.

Figure 1 – proportion of patients with hair regrowth for each dosing strategy (King, et al. 2023 graphical abstract).

After the 24-week extension period, and so 48 weeks of total treatment, the proportion of people achieving significant regrowth rose to 43% for people on the 50mg dose and 31% for people on the 30mg dose. People who had originally received placebo were now also given the highest 50mg dose, and 19% of them achieved regrowth, while 34% of those who also received the 200mg 4-week loading dose achieved significant regrowth. Throughout the study period, and in each of the ritlecitinib dosing groups, over 80% people also experienced increased side effects such as headaches, common colds and infections. The proportion of serious adverse events was very low however.

In conclusion, ritlecitinib at 50mg and 30mg are both effective at regrowing hair (with or without a 200mg loading dose), although the 50mg dose was more effective. The response continued throughout the 48-week period, and the drug was generally safe and well tolerated.

For the full text: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00222-2/fulltext

For the graphical abstract: https://www.thelancet.com/pb-assets/Lancet/infographics/ritlecitinib_alopecia/Ritlecitinib_alopecia_areata.pdf