Accepted Article

DR DAVID ROSMARIN (Orcid ID : 0000-0003-2673-0717)

Article type

: Research Letter

Efficacy of in-class IL-23 inhibitor switching: Risankizumab following Guselkumab failure in moderate-to-severe psoriasis treatment Dear Editor, The development of drugs that target the Th17 axis has had a profound effect on the treatment and management of psoriasis. IL-23 inhibitors in particular, including guselkumab and risankizumab have been shown to be highly effective and have a favorable safety profile.1 Though recent studies have shown that in-class biologic switching can be effective in the treatment of psoriasis, no investigation has assessed the efficacy of an in-class IL-23 inhibitor switch.2,3 We conducted an observational retrospective study in a single medical center at Tufts Medical Center. Data was reviewed for patients with psoriasis who were initially treated with guselkumab (100 mg) and were later switched to risankizumab (150 mg) as well as for patients who were naïve to an antiIL-23 and treated with risankizumab (150 mg). The product of physician’s global assessment and body surface area (PGA*BSA) before and after each medication was used to assess the severity of psoriasis and efficacy of treatment. We defined primary failure as those who did not respond favorably to treatment or who required a switch in initial treatment within the first six months. Secondary failures were characterized as those who initially responded favorably but then lost response. A total of 23 patients who initially failed guselkumab treatment and subsequently switched to risankizumab met the inclusion criteria. Patient demographics, co-morbidities, and previous This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.19575 This article is protected by copyright. All rights reserved

Accepted Article

medication use were all collected for analysis (table 1). Of five patients on the combination of guselkumab and apremilast that were switched, four were to the combination of risankizumab and apremilast with one patient to risankizumab alone. In the group of guselkumab failures, prior to beginning guselkumab, patients had a mean PGA*BSA of 25.8, and the mean PGA*BSA after guselkumab treatment was 27.6. Among these patients, 12 were primary failures and 11 were secondary failures. Prior to starting risankizumab, the mean PGA*BSA was 28.5. After risankizumab treatment, the mean PGA*BSA was 5.9 with a 79.3% average decrease. Of the 23 patients, 21 were still undergoing risankizumab treatment while two were primary failures and switched to other treatments. In a subset analysis of the primary failure guselkumab patients, there was a PGA*BSA of 20.3 before risankizumab treatment and 8.6 after treatment with a 57.6% decrease. For the secondary failure patients, the PGA*BSA was 36.0 before risankizumab treatment and 3.6 after treatment with a 90.0% average decrease. For comparison, there are 18 patients who only underwent risankizumab treatment without a prior switch from guselkumab. Patient demographics, co-morbidities, and previous medication were collected for analysis. The PGA*BSA before risankizumab treatment was 49.8 and after treatment was 7.8 for an 84.3% decrease. The improvement in this study for risankizumab is notably similar to the mean PASI improvement of 90% at week 16 seen from the phase III program. Duration of medication use, concurrent treatments, and treatment outcomes are summarized in Table 1. Overall, our results indicate that patients who fail guselkumab treatment may still respond favorably to risankizumab. Furthermore, patients who failed guselkumab and later switched to risankizumab seem to have a similar response to those that were on risankizumab alone. Though primary failure guselkumab patients seem to have a less effective response to risankizumab than the secondary failure guselkumab patients, there is still a notable reduction in PGA*BSA. Reasons for the difference in response after the medication switch remain poorly understood given that guselkumab and risankizumab are both IL-23 p19 inhibitors.4

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Accepted Article

Some limitations of the study include the retrospective nature of the study, a small sample size, concurrent medication use, and the lack of washout of prior treatments. There was also a shorter follow-up time for detecting secondary failures from the risankizumab group compared to the guselkumab group (average of 5.4 months vs 13.2 months). In conclusion, this study is the first to investigate an in-class IL-23 inhibitor switch from guselkumab to risankizumab. As our results indicate a similar efficacy in treatment response when performing an in-class switch, we hope physicians can expand their toolset when treating moderate-to-severe psoriasis. R. Reddy, S. Pannu, K. Fiumara, J. Kahn, D. Rosmarin Tufts Medical Center, Boston, MA, USA Correspondence: David Rosmarin Email: [email protected] https://orcid.org/0000-0003-2673-0717 (D. Rosmarin)

References 1 Nogueira, M., & Torres, T. (2019). Guselkumab for the treatment of psoriasis–evidence to date. Drugs in Context, 8. 2 Sherman, S., Solomon-Cohen, E., Amitay-Laish, I., Hodak, E., & Pavlovsky, L. (2019). IL-17A Inhibitor Switching–Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience. Acta dermato-venereologica, 99(9-10), 769-773. 3 Georgakopoulos, J. R., Phung, M., Ighani, A., Lam, K., & Yeung, J. (2019). Biologic switching between interleukin 17A antagonists secukinumab and ixekizumab: a 12‐week, multicenter, retrospective study. Journal of the European Academy of Dermatology and Venereology, 33(1), e7e8.

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4 Baker, D. E. (2019). Risankizumab. Hospital Pharmacy. Funding sources: Sukhmani Pannu received a fellowship grant from AbbVie pharmaceuticals. Conflicts of interest: David Rosmarin has received honoraria as a consultant for AbbVie, Celgene, Concert, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB, VielaBio; has received research support from AbbVie, Amgen, Bristol Meyers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals Inc; and has served as a paid speaker for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi.

Table 1: Demographics and characteristics of patients with moderate-to-severe psoriasis Variables

Patients who switched from

Patients who have been on

Guselkumab to

Risankizumab but not

Risankizumab (n=23)

Guselkumab (n=18)

45.0 ± 15.4

44.9 ± 13.0

Male

14 (61%)

11 (61%)

Female

9 (39%)

7 (39%)

White

20 (91%)

14 (78%)

Asian

2 (9%)

3 (17%)

Black

1 (4%)

0 (0%)

Arthritis

5 (22%)

5 (28%)

Depression

5 (22%)

2 (11%)

Anxiety

4 (17%)

2 (11%)

Hypertension

3 (13%)

2 (11%)

Age in years Gender

Race

Co-morbidities

Previous Medication Use

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15 (65%)

4 (22%)

Adalimumab

13 (57%)

9 (50%)

Etanercept

12 (52%)

3 (17%)

Ixekizumab

10 (43%)

2 (11%)

Secukinumab

9 (39%)

5 (28%)

Accepted Article

Ustekinumab

Guselkumab

Risankizumab

Risankizumab

13.2 ± 10.3

5.4 ± 2.6

4.5 ± 3.8

0 (0%)

21 (91%)

18 (100%)

Primary Failure

12 (52%)

2 (9%)

0 (0%)

Secondary Failure

11 (48%)

0 (0%)

0 (0%)

Apremilast

5 (22%)

4 (17%)

1 (6%)

Topical Corticosteroids

5 (22%)

4 (17%)

15 (83%)

PGA*BSA Before

25.8 ± 25.9

28.5 ± 54.7

49.8 ± 54.5

PGA*BSA After

27.6 ± 43.8

5.9 ± 6.9

7.8 ± 18.5

Avg duration in months on treatment Outcome Ongoing

Concurrent Tx

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