On the trail with Sherlock Holmes and CSI - Mystery cases solved

At the “somewhat different” AbbVie Symposium at this year’s Swiss Dermatology Congress (SGDV Congress) in Lausanne, experts did some excellent detective work: a missing person was found and the mysteriously altered behavior of a patient was also clarified. Find out here how Sherlock Holmes and the CSI agent were able to solve the cases at the symposium.

Psoriasis (PsO) and atopic dermatitis (AD) are incurable, inflammatory skin diseases that are caused by a dysregulation of the immune system and place a heavy physical and psychological burden on those affected [1, 2]. With the help of PD Dr. Florian Anzengruber alias “Sherlock Holmes” and Prof. Dr. med. nat. Christoph Schlapbach as a “CSI agent”, the “Director” Prof. Dr. med. Curdin Conrad was able to solve the disappearing symptoms of a PsO patient and the positive change of character of an AD patient. The culprits: risankizumab and upadacitinib.

Wanted: PsO symptoms

Pete Solomon Davies (P.so. D.) is missing – he was last seen with inflamed plaques on his skin and joint pain. In order to find the missing man, Sherlock first diagnosed him with PsO. He found two prescriptions for PsO treatment in his apartment: phototherapy and biologics. He searched for more evidence and came across an analysis that showed that progression to psoriatic arthritis (PsA) was reduced in PsO patients treated with biologics (n = 234) compared to those treated with phototherapy (n = 230) [3]. Progression to PsA was particularly reduced with IL-23 inhibitors (IL-23i) [4]. Patient mortality was also reduced by systemic biologics treatment [5]. After looking at the treatment history of P.so. D. (one administration of “Risa” every 12 weeks), Sherlock now knew that he had been treated with the IL-23i Risankizumab [6]. Risankizumab had shown a sustained response in PsO patients over a period of 5.5 years in the LIMMitless-OLE study [7]. So the mystery was solved: P.so. D. was found, albeit without PsO plaques or joint complaints, but carefree in short summer pants.

Mysterious behavioral change in AD patient

The mother of Abby Dean (A. D.) noticed some unusual changes in her adult daughter’s behavior: she looks different, is no longer tired, goes to work every day, is out and about a lot at weekends and often in short dresses. Are drugs involved here? To get to the bottom of this, the CSI agent first looked at the patient’s diary, in which she complained of severe AD and asthma. He also found empty packages of calcineurin inhibitors and steroids. Fortunately, there was also a biopsy lying around – with an RNA analysis, the diagnosis of “atopic dermatitis” (AD) was made. The agent remembered that JAK1 plays an important role in the pathogenesis of AD [8, 9]. He looked around the scene again and found an opened packet of 15mg upadacitinib with instructions for once-daily dosing [10]. In AD, the quality of life (QoL) of those affected is severely impaired, they are often unable to go to work and develop depression, anxiety or sleep disorders [11, 12]. In two studies, the agent then found that treatment with the JAK inhibitor upadacitinib can significantly reduce itching after just two days and significantly increase QoL in 75% of patients [13]. Sleep problems also decrease after 52 weeks, and up to 4 out of 10 of the treated patients show a clear skin appearance after 16 weeks of treatment (EASI 100) [14]. The case was thus solved: A. D. benefited greatly from the upadacitinib therapy and was thus able to return to an active life.

Conclusion

Thanks to Sherlock Holmes and the CSI agent, the Director now knew that treatment with risankizumab for PsO and upadacitinib for AD had led to symptom freedom and positive personality changes respectively in our mysterious case studies. In order to solve his cases in the future without the two detectives, he noted that early risankizumab treatment can reduce the progression of PsO and upadacitinib therapy can achieve a rapid improvement in skin appearance and QoL in AD patients [7, 13].

The cases presented are hypothetical case studies that were developed with the specialists.

Abbreviations: AD = Atopic dermatitis; IL = Interleukin; JAK = Janus kinase; PsO = Psoriasis; TNF = Tumor necrosis factor; TSLP = Thymic stromal lymphopoietin; QoL = Quality of Life.

Brief technical information SKYRIZI® and RINVOQ®

CH-SKZD-230090_11/2023

This article has been released in German.

This article was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, Cham.

Contribution online since 11.12.2023

Literature

1 Gittler, J.K., et al, Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol, 2012. 130(6): p. 1344-54.
2 Mahil, S.K., F. Capon, and J.N. Barker, Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol, 2016. 38(1): p. 11-27.
3 Gisondi, P., et al, Biological disease-modifying antirheumatic drugs may mitigate the risk of psoriatic arthritis in patients with chronic plaque psoriasis. Ann Rheum Dis, 2022. 81(1): p. 68-73.
4 Singla, S., et al, Association between biological immunotherapy for psoriasis and time to incident inflammatory arthritis: a retrospective cohort study. The Lancet Rheumatology, 2023. 5(4): p. e200-e207.
5 Langley, R.G., et al, Reduced risk of mortality associated with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment and Registry (PSOLAR): A nested case-control analysis. J Am Acad Dermatol, 2021. 84(1): p. 60-69.
6. current expert information ^SKYRIZI® (risankizumab) at www.swissmedicinfo.ch.
7. Papp K et al. Long-term Safety and Efficacy of Risankizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: Interim Analysis of Results From the LIMMitless Open-label Extension Trial Beyond 5.5 Years of Follow-up. Poster 43928. Presented at the 2023 American Academy of Dermatology Annual Meeting (AAD 2023), March 17-21, 2023, New Orleans, LA, United States.
8 Furue, M., et al, Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies.Allergol Int, 2017. 66(3): p. 398-403.
9 Bao, L., H. Zhang, and L.S. Chan, The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. Jakstat, 2013. 2(3): p. e24137.
10. current technical information ^RINVOQ® (upadacitinib) at www.swissmedicinfo.ch
11. Simpson, E.L., et al, Patient burden of moderate to severe atopic dermatitis (AD): Insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol, 2016. 74(3): p. 491-8.
12 Whiteley, J., et al, The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey. Curr Med Res Opin, 2016. 32(10): p. 1645-1651.
13 Guttman-Yassky, E., et al, Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomized controlled phase 3 trials. Lancet, 2021. 397(10290): p. 2151-2168.
14 Simpson, E.L., et al, Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis: Analysis of Follow-up Data From the Measure Up 1 and Measure Up 2 Randomized Clinical Trials. JAMA Dermatology, 2022. 158(4): p. 404-413.