Baricitinib BREEZEs through in atopic dermatitis
In adults with moderate-to-severe atopic dermatitis (AD), use of the oral, selective Janus kinase 1/2 inhibitor baricitinib* led to significant improvements in quality of life (QoL) parameters in AD, accordingly to subgroup analyses results of the BREEZE-AD5 trial.
BREEZE-AD5 randomized 440 participants who had failed topical AD regimens 1:1:1 to receive QD baricitinib 1 or 2 mg or placebo. The subgroup analyses focused on the effect of baricitinib 2 mg at week 16 on various clinical and QoL parameters.
In this subgroup, participants were classified as either itch responders or nonresponders (ie, ≥4- or <4-point Itch Numeric Rating Scale [NRS] improvement, respectively). [AAD 2021, poster 25447]
There were more itch responders in the baricitinib vs the placebo arm (25.2 percent vs 5.7 percent; p≤0.001), signifying the former’s potential to significantly reduce itch, which is the most burdensome AD symptom. [Lancet 2020;396:345-360] “It is thus important for AD treatments to have a rapid onset of action to quickly reduce itch and improve QoL and relieve suffering,” the researchers said.
Compared with itch nonresponders (n=325), responders (n=61) had greater least-squares mean (LSM) change in DLQI** score (–11.7 vs –3.4 percent). There were also more responders vs nonresponders who achieved DLQI 0/1 response*** (37.7 percent vs 1.8 percent) and ≥4-point DLQI improvement (76.3 percent vs 11.5 percent; p≤0.001 for all).
Itch responders vs nonresponders had greater LSM reductions in presenteeism# (–29.3 percent vs –5.6 percent), work impairment (–26.1 percent vs –4.8 percent), and activity impairment (–38.2 percent vs –6.6 percent; p<0.0001 for all), signifying meaningful improvements in work productivity.
In this analysis, there were more baricitinib vs placebo recipients who were able to sleep better (33.0 percent vs 8.6 percent; p≤0.001), highlighting the study drug’s capacity to reduce night-time awakenings due to itch. [AAD 2021, poster 26053]
Compared with sleep nonresponders (n=180), more responders (n=51) had ≥4-point DLQI improvement (60.8 percent vs 6.9 percent), DLQI 0/1 response (25.5 percent vs 1.1 percent), and greater LSM reductions in presenteeism (–33.3 percent vs –6.1 percent), activity impairment (–39.9 percent vs –7.3 percent), and overall work impairment (–34.7 percent vs –5.8 percent; p≤0.001 for all).
Sleep disturbance due to itch is another troublesome AD symptom, which can significantly impair QoL and work productivity. [J Invest Dermatol 2015;135:56-66] “[The findings suggest that] patients who slept better had significant increases in QoL and work productivity vs patients without sleep improvement,” said the researchers.
Another analysis looked into the effect of baricitinib on skin pain (eg, discomfort, soreness), which has emerged as one of the main and most annoying symptoms of AD. [J Drugs Dermatol 2020;19:921-926] Participants were classified as either responders or nonresponders (ie, ≥4- or <4-point Skin Pain NRS improvement, respectively). [AAD 2021, poster 26292]
Skin Pain NRS change from baseline was greater with baricitinib vs placebo (–2.4 vs –1.0; p≤0.01), as was the fraction of participants who achieved ≥4-point Skin Pain NRS improvement from baseline (25.2 percent vs 5.2 percent; p≤0.001).
Of note were the consistent reductions in daily LSM percent change from baseline Skin Pain NRS, which began as early as day 1, constantly dropping until day 7 (–17 percent vs 7 percent; p≤0.001). “[This signifies] rapid reductions in skin pain severity, [which] remained significant through day 7 for both baricitinib doses,” said the researchers.
Compared with Skin Pain NRS nonresponders (n=293), more responders (n=56) achieved ≥4-point DLQI improvement (71 percent vs 10 percent), and had greater LSM change from baseline DLQI total score (–11.1 vs –3.5; p≤0.001 for both).
“[Collectively, these findings imply that] patients with clinically meaningful reductions in [itch, night-time awakenings, and skin pain] were significantly more likely than patients without [these] improvements to achieve clinically meaningful improvements in QoL, report that their skin disease no longer had an impact on their QoL, be more engaged at work, and have less impairment of work and nonwork activities,” said the researchers.