Following a long process of preparation and consultation with different involved groups, the National Institute for Health and Care Excellence (NICE) held a technology appraisal meeting for baricitinib on the 7^th of February.

Baricitinib is a drug (one of the ‘JAK inhibitors’) developed by the pharmaceutical company Eli Lilly. Also known as Olumiant, it has already been granted marketing authorisation for the treatment of severe alopecia areata (AA), by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). This means that they have deemed the drug safe and effective for the treatment of severe AA in adults, and it is allowed to be sold and used in the UK for this purpose.

Currently, it is only available to adults with AA privately (but not on the NHS). However, it is already being used by the NHS to treat other conditions, such as rheumatoid arthritis and COVID. Whether the NHS decide to also supply baricitinib for adults with severe AA, will depend on the NICE process. A large part of this is based on resource and cost-effectiveness: will it be worth it for the NHS to give baricitinib to people with AA? 

The technology appraisal meeting was attended by:

• Representatives from Eli Lilly, the pharmaceutical company producing baricitinib;
• Members of the external assessment group (EAG), independent, external experts tasked with evaluating the basis for use of this treatment;
• Clinical expert dermatologists Dr Matthew Harries and Dr Abby MacBeth;
• Sue Schilling, Alopecia UK CEO and Lynn Wilks, Alopecia UK Trustee, to represent the patient perspective.
• Members of the NICE technology appraisal committee, who evaluate all the submissions and advise on whether this new drug will be worth supplying on the NHS;

“The technology appraisal committee is an independent standing committee that produces recommendations. They consider the evidence and make a judgement on whether or not the technology should be recommended as a clinically and cost-effective use of NHS resources, or whether it should only be recommended for specific indications or subgroups of patients.”

To give you a better idea of why this is such an important moment, we will summarise the process and discuss the research evidence underpinning the use of baricitinib for hair regrowth.

First, what does the NICE process look like?

The technology appraisal meeting is part of a larger process that started in January 2022. In the lead-up, the pharmaceutical company, clinical experts, and patient representatives submitted materials to provide evidence and outline the current state of affairs. To make a well-informed decision, the committee wants to know for example:

• What treatments are currently available for patients?
• What are their costs?
• In what situations do they get which treatments (e.g. depending on disease severity)?
• How does this treatment compare to other available treatments?
• Where would this new treatment fit in the typical treatment pathway?
• How does AA affect well-being and quality of life for patients?

In the meeting itself, many aspects of baricitinib were discussed, such as the scientific basis for its use, treatment pathway, patient perspectives, clinical perspectives, and cost effectiveness. This allowed the experts to clarify and emphasise the materials they had submitted prior to the meeting.

One of the discussion points was around how baricitinib treatment compares to other treatment options. It was noted that contact immunotherapy is currently one of the best options, but this is available only in specialist clinics and therefore not accessible to many patients. As there are currently no licensed treatments for AA supplied by the NHS, it is hard to make direct comparisons between these unlicensed treatments and baricitinib. We also know that treatment pathways can look vastly different for different people and in different areas, and it was suggested this is currently a bit of a ‘postcode lottery’. It is likely that the introduction of baricitinib would create big changes in treatment pathways.

The last point on well-being and quality of life is where Alopecia UK played an important role, as we represent the collective voice of the alopecia community. Through our work to understand how AA impacts people’s lives, we were able to give evidence of how it significantly affects emotional well-being, ability to work, study, socialise, ability to take part in leisure activities, intimate relationships, and finances. In addition, we know that people with AA experience high rates of anxiety and depression. Those with alopecia totalis or universalis may also experience physical symptoms related to temperature regulation, nasal secretions, and eye strain. Further, there are currently no licenced products for treatment of AA, and the treatment landscape is very variable with people across the country all having different experiences. Many people, including GPs, still see AA as just a cosmetic issue, and don’t understand the full gravity of the condition. Through our submissions of data and personal stories, we were able to show that AA has serious consequences on many aspects of people’s lives. Our argument is that besides individuals being affected personally, AA also results in pressure on, and costs for, the NHS, which could potentially be avoided by treatment with baricitinib.

What is the scientific evidence for the use of baricitinib for hair regrowth?

The committee also considers the scientific evidence supporting the use of baricitinib for adults with AA, as it shows how likely people are to achieve hair regrowth with this treatment.

There have been two large-scale clinical trials for using baricitinib in adults with alopecia areata: BRAVE-AA1 and BRAVE-AA2. BRAVE-AA1 started as a small scale phase-II clinical trial (guidance from Cancer Research UK on clinical trial phases) with 110 participants, who received baricitinib at 1mg, 2mg, 4mg or placebo for 36 weeks to evaluate the best dose for hair regrowth with no adverse side effects (phase-II results only). Participants were those with severe alopecia areata (≥50% scalp hair loss, current episode >6 months but <8 years, and no spontaneous improvement in last 6 months). After 36 weeks, 33.3% of people on 2mg/d baricitinib, and 51.9% of people on 4mg/d baricitinib had hair regrowth to the point where less than 20% of their scalp was affected by hair loss. This was measured using the Severity of Alopecia Tool (SALT) score, which measures the total scalp area affected by hair loss, and so would be written as SALT ≤20.

The 1mg dose was then dropped, as it was ineffective, and the trial was adapted into a phase-III clinical trial to test the 2mg and 4mg doses against placebo in a different, larger set of people (654 participants with severe AA). A second phase-III trial (BRAVE-AA2), identical to the phase-III part of BRAVE-AA1 included another 546 people with severe AA. The results of both trials were published in The New England Journal of Medicine in May 2022. In total, people from 169 centres in 10 countries were studied. Again, the threshold for success was set as SALT ≤20 at week 36 of treatment (i.e., ≥80% scalp coverage). From 654 participants in BRAVE-AA1, 38.8% of people on 4mg baricitinib achieved a SALT ≤20, 22.8% of those on the 2mg dose, and 6.2% of people on placebo also did. In BRAVE-AA2, this was 35.9% for 4mg, 19.4% for 2mg, and 3.3% for placebo. So, in BRAVE-AA1 the difference between 4mg baricitinib and placebo was 32.6 percentage points (i.e., 38.8%-6.2%), and the difference between 2mg baricitinib and placebo was 16.6 percentage points. In Brave-AA2 these values were 32.6 and 16.1. So, the 4mg dose was superior to placebo in achieving SALT ≤20 in about one third of people. The 2mg dose was superior to placebo in achieving SALT ≤20 in about one sixth of people.

In terms of side effects, common ones observed with baricitinib treatment included acne, upper respiratory tract infections, urinary tract infections, headaches and elevated creatine kinase levels (measure of muscle damage found in blood). The researchers also observed elevated levels of LDL cholesterol in 25%, and elevated levels of HDL cholesterol in 40%, of people who received baricitinib. The participants continued to be monitored after the 36 week period of treatment, and further details on the safety profile of baricitinib were recently published in the British Journal of Dermatology. This analysis combined the data from the phase-II and both phase-III trials (1303 participants in total) and confirmed that the safety profile of baricitinib is consistent over a longer timeframe. They will also continue to monitor patients for up to 200 weeks to further study long-term effects.

What about quality of life?

We know that hair loss has a large impact on people’s emotional well-being and ability to engage with society. It can therefore be expected that hair regrowth would bring improvements in these domains. In the BRAVE-AA trials, participants were asked to fill in surveys to evaluate their emotional well-being and quality of life. However, unfortunately this data is not publicly available at this time. At the meeting, some time was spent discussing the different measurements used to assess quality of life, and comparisons were made between different studies. The pharmaceutical company also submitted evidence on quality of life from a study they had funded themselves (Adelphi study), but this data is also not publicly available.

Other scientific considerations

A threshold of 20% scalp hair loss was chosen as a ‘clinically meaningful’ outcome in the BRAVE-AA trials. Meaning, people who did not achieve more than 80% scalp hair cover after 36 weeks were not seen as successes, even if they did achieve a significant amount of hair regrowth. The concept of clinically meaningful is used because we want to have a clearly defined rule to say whether the treatment is worth it or not. But, how do you decide where this threshold lies? Using SALT ≤20 at 36 weeks of treatment as the cut-off point for a decision on whether the treatment was successful or not can be seen as overly restrictive. For some people, a reduction in SALT to ≤50 can be very meaningful, if they started at 90-100% hair loss. In some people, it may also be that baricitinib treatment can induce full hair regrowth, but requires longer than 36 weeks. Additionally, hair may regrow, but because there is also pattern balding, baricitinib is unable to induce hair growth to SALT ≤20. There was some discussion at the meeting about the use of SALT as a relative score (e.g., SALT₅₀ would be a 50% reduction in SALT score from SALT 80 to SALT 40). However, the clinicians suggested they prefer to use the SALT score as an absolute value as it is easier to understand for patients.

It should also be noted that SALT score does not take into account hair loss in areas other than the scalp. In a separate publication, the authors of the BRAVE trials show that a proportion of the people who did not achieve SALT ≤20 at week 36 did experience regrowth of eyebrow and eyelashes. Beyond the cosmetic aspect, hair also performs important bodily functions, such as in temperature regulation, nasal secretions and shielding of the eyes. So, even if treatment does not lead to a full head of hair, regrowth of hair on other parts of the body can be meaningful and important too.

Another consideration the committee have to make is how the populations studied in the BRAVE trials may differ from those that would receive baricitinib in the UK. The BRAVE-AA trials included participants from USA, Japan, Korea, Mexico (BRAVE-AA1); and Argentina, Australia, Brazil, China, Israel, Japan, Korea, Taiwan, and USA (BRAVE-AA2). Notably, these studies did not include people from the UK. Ethnicity likely plays a role in the onset and development of AA, and so might also affect how effective baricitinib is in treating it. However, at the meeting, the experts agreed that the population who would receive this treatment in the UK are similar to the populations studied in the BRAVE-AA trials. So, the effects of treatment would likely also be similar for people in the UK.

What now?

The committee decision is expected on 21 June 2023. Baricitinib is one of many JAK inhibitors currently being developed by different pharmaceutical companies, and is the first to be assessed by NICE. Other JAKs may undergo a similar process in the future too. However, while the prospect of this new treatment (and possibly others) to regrow hair is exciting, expectations should be managed, as the research showed it does not work for everyone. The research also showed that there can be side effects. Finally, if it does get approved, it would only be available for adults with severe AA.