Deuruxolitinib helps restore crowning glory in alopecia areata

Pooled analyses of the phase III THRIVEAA1 and THRIVE-AA2 trials underpin the potential of the selective oral JAK* 1/2 inhibitor deuruxolitinib to effectively and safely reverse hair loss in adults with moderate-to-severe alopecia areata (AA).

The two trials comprised a total of 1,220 patients who had ≥50 percent scalp hair loss and current AA episode >6 months and <10 years (safety cohort). They were randomized to receive deuruxolitinib 8 mg BID (n=606) or 12 mg BID (n=344) or placebo (n=270) for 24 weeks.

Efficacy outcomes

In the efficacy analysis (n=1,209), deuruxolitinib treatment led to significant dose-dependent scalp hair regrowth, as reflected by the higher percentage of deuruxolitinib recipients achieving a SALT** score ≤20 at week 24 vs those on placebo (31 percent [8 mg] and 40 percent [12 mg] vs 0.8 percent; p<0.0001 for both comparisons). [AAD 2024, abstract 51840]

Significant differences were also observed between deuruxolitinib (both doses) and placebo as early as week 8 (p<0.0005), which continued to improve until week 24.

A similar trend favouring deuruxolitinib over placebo was seen in terms of the percentage of patients achieving a SALT score ≤10 at week 24 (22 percent [8 mg] and 32 percent [12 mg] vs zero percent; p<0.0001 for both).

“The relative change in mean SALT score from baseline were significant for both [deuruxolitinib] dose groups vs placebo as early as week 4,” the researchers noted. This means that scalp hair regrowth started early on. This trend continued that by week 24, the relative changes were –43 percent and –51 percent for deuruxolitinib 8 and 12 mg, respectively, and zero percent for placebo (p<0.0001 for both comparisons).

“[Moreover, there was] a significant proportion of patients achieving reductions in SALT score of ≥40,” they added.

Both deuruxolitinib doses met the primary efficacy endpoint of SALT score ≤20, which has been shown to be clinically meaningful for patients and hair experts. [Br J Dermatol 2020;183:702-709]

“Without effective treatment, many individuals with AA will have persistent multifocal recurrent disease, and some may progress to more severe forms,” they said. “These efficacy results are encouraging and support further development [of deuruxolitinib] for the treatment of moderate-to-severe AA.”

Safety profile

The most common treatment-emergent adverse events (TEAEs) in the deuruxolitinib arms were COVID-19 (13 percent), headache (12 percent), and acne (10 percent). Of the serious TEAEs reported, three were deemed related to the study drug (occurred in two patients): meningitis, pyrexia, and influenzal pneumonia. [AAD 2024, abstract 54022]

“TEAEs related to potentially significant laboratory anomalies only occurred in a small number of patients. There were no clinically meaningful treatment group trends with regard to vital signs and ECG results,” said the researchers.

Taken together, both deuruxolitinib doses were generally well tolerated. “These data reinforce the concept that the overall safety profile of deuruxolitinib is encouraging in patients with AA, which is consistent with the known safety profiles of other JAK inhibitors,” they said.

Patient-reported outcomes

Using data from the efficacy cohort, more patients on deuruxolitinib reported being ‘satisfied’ or ‘very satisfied’ (on the Hair SPRO*** scale) with their scalp hair following treatment vs those on placebo by week 24 (44 percent [8 mg] and 52 percent [12 mg] vs 3 percent; p<0.0001 for both comparisons). [AAD 2024, abstract 54029]

Results were also better with deuruxolitinib vs placebo in terms of PGI-S^# (mean score 4.5 [8 mg] and 4 [12 mg] vs 6.4) and PGI-I^# (54 percent and 67 percent vs 6 percent; p<0.0001 across all comparisons).

In the PGI-S 7-point scale, lower scores denote better outcomes (1 corresponds to ‘normal, no hair loss’ while 7 denotes the ‘most extreme hair loss’). For PGI-I, the percentage of responders pertains to those who reported that their hair was ‘much improved’ or ‘very much improved’.

“AA leads to reduced quality of life and a considerable psychosocial impact for patients … [These] results demonstrate the wider clinical benefit of deuruxolitinib on patient satisfaction,” said the researchers.