Optimising safety of JAK inhibitors for alopecia areata
By Yomna Nassar
Brittany Craiglow (Yale University School of Medicine, New Haven, Connecticut, USA) gives her perspective on optimising JAK inhibitors for alopecia areata. View transcript.
Speaking in a session on new therapies for alopecia areata (AA), Brett King (Yale University, School of Medicine, New Haven, Connecticut, USA) noted that AA, like any other chronic inflammatory disease, requires long-term treatment, and stressed: “There is a tremendous need for effective treatments in inflammatory skin diseases, and JAK inhibitors have the potential to treat diseases across the spectrum of inflammatory diseases.”
He added: “JAK inhibitors have changed dermatology and will continue to change in ways that no other class of drugs has or presently can do.”
However, King pointed out that some of the key safety data for JAK inhibitors, which resulted in a black-box warning, came from the ORAL post-marketing surveillance of tofacitinib versus tumour necrosis factor inhibitors in people with rheumatoid arthritis who were relatively old with a high BMI, and were taking methotrexate and concomitant corticosteroid medication.1
“The idea here is that you can’t extrapolate the statistics to a 35-year-old patient with severe AA who does not have a cardiovascular event”, said King.
He pointed out that no study has investigated the adverse events of JAK inhibitors in dermatologic diseases, but suggested that to optimise safety it is important to use caution in people who are older than 65 years, obese and are current or past smokers. Caution is also needed when treating people with AA who have a history of diabetes, coronary artery disease, thromboembolism, inherited coagulation disorder or malignancy other than treated non-melanoma skin cancer.
Additionally, before starting JAK inhibitor treatment, King advised to screen people with AA for tuberculosis and hepatitis B and C, and closely monitor them while on treatment, with a periodic full body skin examination, and to follow vaccination guidelines.
Looking specifically at baricitinib, King explained how understanding the patterns and likelihood of adverse events in different patient populations can help healthcare providers assess the benefit-to-risk ratio for individual patients.
Overall, the rates of infections and other adverse events with baricitinib were generally aligned with the underlying risks associated with the diseases being treated:
Serious infections were more common in rheumatic diseases than in dermatological disorders
Rates of cardiovascular events and malignancies were generally within or below the ranges reported for these disease populations
Adverse events were more common in patients with specific risk factors for each event. When compared with other medications like tofacitinib, baricitinib showed similar or lower rates of adverse events
Ritlecitinib and deuruxolitinib for alopecia areata
Ritlecitinib
Brittany Craiglow gave an overview of the latest data on ritlecitinib, which was approved in 2023 for the treatment of severe AA in people aged 12 years and older. This was based on data from the ALLEGRO trial showing a treatment response (Severity of Alopecia Tool [SALT] score ≤20) in 23% of participants after 24 weeks of treatment and 43% after 48 weeks.2
Brittany Craiglow provides an analysis of the ALLEGRO trial and its implications for clinical practice. View transcript.
Longer-term data from a pooled analysis of trials in the ALLEGRO programme showed that, during up to 24 months of follow-up, 54.3% of adolescents and adults with alopecia but not alopecia universalis achieved a response, as did 36.1% of those with alopecia universalis.
Deuruxolitinib
Brett King provided an update on phase 3 data for the investigational treatment, deuruxolitinib. In the THRIVE-AA2 trial, the proportion of patients achieving a SALT score of 20 or lower was 48.8% at week 68 of treatment. He explained that the results plateau at 52 weeks, although some participants achieved a response up to weeks 55 and 68.
King, 2023. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. https://www.doi.org/10.1016/s0140-6736(23)00222-2
Predictors of treatment response in alopecia areata
By Yomna Nassar
Brittany Craiglow (Yale University School of Medicine, New Haven, Connecticut, USA) covers predictors of treatment response in alopecia areata. View transcript.
In another session, Brett King (Yale University, School of Medicine, New Haven, Connecticut, USA) highlighted two key factors that influence treatment for alopecia effectiveness:
The first is the presence of hair (versus no hair) at treatment initiation. King cited results showing that the response rates (Severity of Alopecia Tool [SALT] ≤20) to 52 weeks of baricitinib 4 mg were 27.7% for people with 95–100% scalp hair loss at baseline versus 51.2% for those with 50–95% scalp hair loss. This shows that treatment is more effective in patients before total scalp hair loss occurs
The second factor is the duration of the current episode of severe scalp hair loss. Response rates after 52 weeks of treatment were 27.3% for people with severe scalp loss for more than 4 years compared with 48.6% of those with severe alopecia areata (AA) lasting for no more than a year
Relationship between alopecia areata and exacerbations
King said that if people with AA continue baricitinib treatment for a year, hair regrowth is maintained. Conversely, the disease flares within weeks or months when medication is stopped, and this can be fast and severe. Moreover, regrowth of hair after resuming treatment may take months and, in rare cases, may not happen at all.
Additionally, if baricitinib is tapered abruptly from 4 mg to 2 mg, disease flare may occur over several weeks or months. Again, it may take months for the person with AA to regrow their hair if they resume their prior dose of the JAK inhibitor. Twice as many people grow hair with the 4 mg versus the 2 mg dose, and the two doses have a similar safety profile, so King said that to grow hair faster, dermatologists use the 4 mg dose.
Severe AA does not wax and wane like moderate and mild AA; only 2.3% of people with severe AA have spontaneous remission over 36 weeks if they do not take baricitinib. King therefore advised that patients with severe AA continue the dose they are taking even after achieving hair regrowth without the need to taper it.
He summarised: “In case you decide to taper after regrowth, make small changes or decreases in the dose and continue the smaller dose for a least 4 months before considering another small dose.”
“If you don’t succeed with one, use the other one; we will have data in a short time showing a large series that failure in one JAK inhibitor does not predict failure in another one”
Psychosocial needs in children with alopecia areata
By Yomna Nassar
Brittany Craiglow (Yale University School of Medicine, New Haven, Connecticut, USA) discusses the psychosocial impact of alopecia areata on young people and children, and the importance of providing effective support. View transcript.
Brittany Craiglow stated that alopecia areata (AA) is “traumatic”. A patient she treated observed that losing their head hair “was very scarring to me; I became extremely self-conscious”.
It took a toll on me mentally. I became hateful towards myself. I stopped showing up to school because I was worried about what people would think of me.”
Young person with AA
The young person said that they were “…caught up in my head a lot, especially when I was alone. I remember all the restless nights crying…and questioning, why me?”
After the young person received JAK inhibitor treatment for AA, they said the treatment “has changed my life. I was extremely suicidal, and this medicine saved me”.
Craiglow therefore stressed the need to attend to young people’s psychosocial needs, in addition to selecting the most suitable medication and treatment plan.
“AA patients need to be validated”, Craiglow noted. “Take time in the office to see how your patients are doing and permit them to say how hard it is. Most are 10 on the feeling scale.”
She said that patients with AA in her office get positive reinforcement for coping. However, evidence that they are coping with the disease does not mean that they would not like their hair to grow back. Craiglow explains that “our job is to bring the two sides together”.
Brittany Craiglow discusses setting expectations and navigating emotions for young people with alopecia areata.View transcript.
Brittany Craiglow shares her own highlights from AAD 2024. View transcript.
Developed by EPG Health. This content has been developed independently of the sponsor, Pfizer, who has reviewed the content only for scientific accuracy. EPG Health received funding from the sponsor in order to help provide healthcare professionals with access to the highest quality medical and scientific information, education and associated relevant content.
