Atopic dermatitis and psoriasis often place a physical and psychological burden on sufferers [1, 2]. At this year’s Swiss Derma Day in Lucerne and at the virtual SSAI Allergology & Immunology Update, three experts from Inselspital Bern gave an overview of current treatments, going into more detail about the efficacy and safety of various JAK inhibitors and biologics.
Due to the complex and multifaceted pathophysiologies of psoriasis (PSO) and atopic dermatitis (AD), treatment options for these inflammatory dermatoses have long been limited to topical or systemic steroids, calcineurin inhibitors, or immunosuppressants [3-5]. However, thanks to modern research and a better understanding of the diseases, the range of therapies for both diseases has expanded significantly in recent years. In the meantime, various biologics can be used for moderate to severe PSO [6] – Prof. Dr. med. Nikhil Yawalkar from the Inselspital Bern even spoke of the “golden age” of psoriasis therapy at the Swiss Derma Day (January 12-13, 2022) [7]. For the treatment of patients with moderate to severe AD, the biologic dupilumab (Dupixent®) and the two Janus kinase inhibitors (JAKi) upadacitinib (Rinvoq®) and baricitinib (Olumiant®) are currently available [8-10]. The latter was presented by Prof. Dr. med. et phil. nat. Christoph Schlapbach at the Swiss Derma Day [4]. Prof. Dagmar Simon, MD, PhD, addressed the SSAI Allergology & Immunology Update, which was held this year by the 28. until January 29 online, both the JAKi and biological treatment approaches to AD [11].
PSO patients with complete skin healing with risankizumab. [12]
PSO is a heterogeneous disease that involves a high impairment of quality of life, and is characterized by comorbidities, such as depression, inflammatory bowel disease, or cardiovascular disease [6, 13, 14]. Since 2000, several cytokine antagonists have been approved that improve the treatment of psoriasis, including TNF, IL-12/IL-23, IL-17, and IL-23 inhibitors [15-22]. According to Prof. Yawalkar, the IL-23 and IL-17 antagonists in particular, for which there are many short-term data, showed high efficacy. For example, the selective IL-23 inhibitor Risankizumab (Skyrizi®) is an extremely effective drug [7]. In the randomized, double-blind, controlled Phase III UltIMMa-1 and -2 trials, approximately 75% of patients with moderate-to-severe PSO achieved at least 90% improvement in the Psoriasis Area and Severity Index (PASI 90) at week 16 after two 150 mg doses of risankizumab at weeks 0 and 4. A PASI 100 response, i.e., complete skin healing, was achieved by 36% (UltIMMa-1) and 51% (UltIMMa-2) of patients, respectively, in the risankizumab arm [12].
Long-term efficacy of risankizumab in the LIMMitless study. [23]
Long-term data on the effects of biologics, on the other hand, are less common, Prof. Yawalkar noted, praising the high response seen with risankizumab, which was stable for 4.5 years in the phase II/III LIMMitless open-label extension study [7, 23]. In this study, 897 patients with moderate-to-severe PSO continued to receive 150 mg risankizumab every 3 months after completion of one of the baseline studies (UltIMMa-1, UltIMMa-2, IMMvent, SustaIMM, or NCT03255382). After 232 weeks, 84% of patients on risankizumab therapy showed a PASI 90 response and 52% showed a PASI 100 response(Figure 1) [23]. The safety profile of the treatment was also favorable, as evidenced by good “drug survival,” Prof. Yawalkar emphasized [7, 15]. In view of the fact that biologics are administered for life as long as there is no modification of the disease course (“deep remission”), this seems to be of particular importance [7, 24].
Figure 1: Efficacy of risankizumab over 232 weeks in moderate-to-severe plaque psoriasis in the LIMMitless open-label extension study. mNRI = modified nonresponder imputation. aDue todifferences in the lengths of the baseline studies, some patients crossed over to the LIMMitless study after less than 52 weeks. PASI 90: 90% improvement in Psoriasis Area Severity Index. Adapted from [23].
JAKi in AD: upadacitinib [9]
At the Swiss Derma Day 2022, Prof. Schlapbach went into more detail about JAKi as a therapeutic option for inflammatory dermatoses. Right at the beginning of his talk, he clearly demonstrated that there was probably no inflammatory disease in which cytokines did not play an essential role and explained the function of JAK molecules in cytokine signaling cascades [4]. Considering the complex biology, it is clear that the molecule JAK1 in particular is of great importance in AD [25, 26].
Among others, Prof. Schlapbach focused on the selective JAK1 inhibitor upadacitinib as a currently approved oral treatment option for moderate-to-severe AD [4, 9]. In the randomized, double-blind, placebo-controlled phase III AD Up trial, 40% of patients with moderate-to-severe AD achieved an validated Investigator Global Assessment (vIGA) score of 0 or 1; under placebo + TCS, it was 11% (p<0,0001) [27].
Efficacy of upadacitinib monotherapy over one year [28]
Prof. Simon also addressed upadacitinib in AD at the 24th SSAI Allergology & Immunology Update later in January 2022. Among other things, she presented the results of the randomized, placebo-controlled phase III MEASURE Up-1 and -2 trials involving a total of 1683 patients, in which upadacitinib was used as monotherapy in moderate-to-severe AD. Prof. Simon emphasized that after 16 weeks, more than 40% of patients taking upadacitinib 15 mg 1x daily achieved an EASI 90 response and significant relief of pruritus. In the placebo groups, only about one in ten patients succeeded in both [11, 29]. After 52 weeks, in an integrated analysis of the two studies, 62% of patients on upadacitinib showed an EASI 90 response and 65% showed significant improvement in pruritus(Figure 2) [28]. In addition, treatment with upadacitinib was associated with a rapid response: improvement in pruritus was observed after only 2 days [29].
Figure 2: Efficacy of upadacitinib (15 mg) over 52 weeks in moderate-to-severe atopic dermatitis in the two ongoing randomized phase III studies, MEASURE Up-1 and MEASURE Up-2. In the first 16-week double-blind phase, patients received either upadacitinib or placebo 1x daily; subsequently, all patients were treated with upadacitinib. Integrated data from MEASURE Up-1 and -2, intention-to-treat (ITT) population, observed case analysis. EASI 90: Improvement in Eczema Area and Severity Index by ≥90%. WP-NRS: Worst Pruritus Numerical Rating Scale. Adapted from [28].
Stable safety profile of upadacitinib [28, 30].
Both the combination of upadacitinib and TCS and upadacitinib as monotherapy were well tolerated over 52 weeks, and no new safety signals emerged compared with the known safety profile of upadacitinib [28, 30]. The most common adverse effects observed with upadacitinib in AD are upper respiratory tract infections, acne, herpes simplex, creatine phosphokinase (CPK) elevations, and headache [9]. According to Prof. Schlapbach, it is still too early to make a statement about malignancies. For all JAKis, he also recommended laboratory controls in case of cardiovascular risk factors or thromboembolism [4].
Conclusion
The modern therapeutic approaches for PSO and AD presented by the experts of the Inselspital Bern show good efficacy. They mean “relief for patients to have more than just TCS, calcineurin inhibitors and cyclosporine,” as Prof. Simon put it at the SSAI Allergology & Immunology Update. In moderate-to-severe PSO, the IL-23 inhibitor risankizumab stands out with stable long-term efficacy [23] and the JAKi upadacitinib achieved rapid and sustained improvement in skin texture and itch in moderate-to-severe AD both as monotherapy and in combination with TCS [28, 30]. Risankizumab and upadacitinib are also characterized by a favorable and known safety profile [23, 28], so patients with moderate-to-severe PSO and AD, respectively, can hopefully benefit from each treatment option in the long term [9, 15].
References
The references can be checked by specialists at medinfo.ch@abbvie.com can be requested.
Text: Dr. sc. nat. Katja Becker
This text was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, 6330 Cham.
To the brief technical information of SKYRIZI® and RINVOQ®.
CH-RNQ_AD-220017_03/2022
Contribution online since 29.03.2022
