Introduction
Upadacitinib (UPA) is a novel, highly selective Janus kinase 1 inhibitor that has received regulatory approval for moderately to severely active ulcerative colitis (UC) and for moderately to severely active Crohn’s disease (CD). Acne was one of the most frequently reported adverse events (AE) in the pivotal trials of UPA for UC and CD and was the most commonly reported AE in our large prospective real-world experience. However, risk factors for this AE are not known. Here we present the real-world experience of patient-reported acne as an AE in patients with inflammatory bowel disease (IBD).
Aims & Methods
We performed a prospective, real-world analysis of incidence of acne in patients receiving UPA for IBD at our institution. Clinical follow-up to assess effectiveness and safety occurred at predetermined intervals during weeks 0, 2, 4, 8, and 12. This included standard questions about extra-intestinal manifestations or AEs, including acne. Disease-, drug-, and patient-related variables were assessed related to acne occurrence. Analysis of covariance (ANCOVA), Shapiro-Wilk normality test, Mann-Whitney test, and multivariate logistical regression (MLR) were performed for predictive variables. Time (in days) to acne occurrence was analyzed using a quartile analysis.
Results
A total of 119 patients with IBD were assessed for the first 3 months on UPA (63 UC, 44 CD, 5 IBD-U, 6 pouchitis (P)); 109 receiving 45 mg/d; 10 receiving 15 mg/d). 35 patients (29%; 23 UC, 10 CD, 1 IBD-U, 1 P all receiving 45 mg/d) reported an AE of acne primarily of the face, but also involving the scalp and back. Treatment discontinuation due to the acne occurred in only 2 patients (5.7%). Of acne-reporting patients, the median time from initiation of UPA to occurrence of acne was 31 days (IQR: 18-49). MLR of all examined variables (AUC=0.6737) demonstrated age stratified by decade (P=0.047) significantly correlated younger age with incidence of acne. Female sex (P=0.08), type of IBD (P=0.11), smoking status (P=0.16), and use of concomitant immunomodulator therapy (P=0.58) or concomitant corticosteroids (P=0.67) were not related to the development of acne on UPA (Table 1).
Table 1. Results of multivariate linear regression for acne observed in IBD patients (n=119) treated with upadacitinib (UPA).
| No acne | Acne reported | P |
| Time to acne reported (days) – median (IQR) | | 32 (18-49) |
|
| UPA dose at acne development 15 mg – n (%) | 10 (11.9) | 0 |
|
| UPA dose at acne development 45 mg – n (%) | 74 (88.1) | 35 (100.0) |
| No concomitant steroid use at UPA initiation – n (%) | 78 (92.9) | 31 (91.2) |
|
| Age (decade) – median (IQR) | 37 (27-46) | 33 (25-42) | 0.047 |
| Female sex – n (%) | 37 (44.1) | 20 (58.8) | 0.080 |
| Never smoking – n (%) | 71 (84.5) | 28 (80.0) | 0.161 |
| Current smoking – n (%) | 3 (3.6) | 2 (5.9) | 0.161 |
| Concomitant steroid use at UPA initiation – n (%) | 38 (45.2) | 15 (42.9) | 0.674 |
Conclusion
In our large real-world experience in patients with IBD treated with upadacitinib, we report a 29% incidence of acne which mostly occurred within the first 31 days of treatment, only with the 45 mg/d dose, and in younger patients. Concomitant steroids or immune therapies were not associated with increased risk of acne. These findings are of considerable interest, and will assist in patient communication and inform a prospective prevention trial for this AE.
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Disclosure
NKC, DKC, SF, NMG, have no relevant disclosures.
DTR has received grant support from Takeda; and has served as a consultant for AbbVie, Alimentiv Inc., Altrubio, Amgen, Arena Pharmaceuticals, Aslan Pharmaceuticals, Boston Consulting Group, Boehringer Ingelheim Ltd., Bristol-Myers Squibb, Buhlmann Diagnostics Corp., Celgene, ClostraBio, Connect BioPharma, Datos Health, EcoR1, Ferring Pharma, Genentech/Roche, Gilead Sciences, IBD RPM dba Chronicles Health, IAG, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Lilly Eli & Co, Menten AI, Pfizer, Prometheus Biosciences, Reistone Biopharma, Sangamo Therapeutics, Shanghai Pharma Biotherapeutics USA, Syneos, Takeda, Target RWE, Techlab Inc., Trellus Health.
