Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for Crohn's disease (CD), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate/loss of response. Factors associated with VDZ dose escalation from Q8W to Q4W and real-world outcomes remain underexplored.

Aims & Methods

Adults with moderate to severe CD initiating VDZ Q8W maintenance therapy were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance therapy any time after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without dose escalation (Q8W maintenance). Baseline characteristics were summarized as median (range) and frequency (%) and compared between cohorts. Rates of clinical remission (Harvey-Bradshaw Index [HBI]<5) were described stratifying by prior biologic experience. Associations between baseline factors and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after treatment initiation and dose escalation were evaluated in the Q8W>Q4W cohort using Kaplan-Meier survival analysis.

Results

250 patients were included in the Q8W>Q4W maintenance cohort (39% bio-naïve), and 116 in the Q8W maintenance cohort (51% bio-naïve). In both cohorts, median age at treatment initiation was 50 years and baseline HBI score was 10. In the Q8W>Q4W maintenance cohort, median disease duration prior to initiation of treatment was 14 years (0-69) and median follow-up duration was 22 months (7-60). In the Q8W cohort, median disease and follow-up duration were 8 years (0-50) and 35 months (27-46), respectively. At 14 weeks post-treatment initiation, rates of remission in the Q8W>Q4W maintenance cohort were 47% (bio-naïve) and 22% (bio-experienced), and in the Q8W cohort 61% (bio-naïve) and 48% (bio-experienced) (Table 1). Among patients in the Q8W>Q4W maintenance cohort not in remission at the time of dose escalating, 33% achieved remission 3 months after dose escalation to Q4W. Disease duration at baseline was shorter in these patients than in those who did not achieve remission (8 months [0-52] vs. 16 months [0-69], p=0.007). In the Q8W>Q4W maintenance cohort, 12- and 24-month treatment persistence after treatment initiation was 91% and 64% (bio-naïve) and 94% and 67% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 66% and 59% (bio-naïve) and 69% and 53% (bio-experienced) (Table 1).

Conclusion

Patients with CD who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of clinical remission than those remaining on Q8W treatment, and one third achieved clinical remission 3 months after dose escalating. Baseline disease duration was significantly associated with remission among those escalating to Q4W.

References

N/A

Disclosure

AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda. AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Janus kinase (JAK) inhibitors have emerged as an important therapeutic class for the management of several immune-mediated conditions, including inflammatory bowel disease (IBD), but they are associated with several side effects. A renewed attention to the safety profile of this drug class has been driven by increasing reports of JAK inhibitor-induced acneiform eruptions seen in clinical trials and real-life practice.

Aims & Methods

We aimed to investigate the epidemiology, clinical characteristics, and treatment outcomes of this condition in patients with IBD. This was an international, multicenter, retrospective cohort study that consecutively enrolled patients with IBD who were treated with JAK inhibitors and subsequently developed acne. The primary objective was to evaluate the clinical characteristics of acne presentation. Secondary objectives included determining acne prevalence, assessing its impact on quality of life, and evaluating the effectiveness of treatments.

Results

Of the 2,183 JAK inhibitor-treated patients with IBD screened, 272 developed acne and were included in the study. The crude prevalence rates of acne were 15.9% for upadacitinib, 4.3% for tofacitinib, and 1.9% for filgotinib, with dose-dependent relationships observed for upadacitinib and tofacitinib. Acne predominantly affected patients aged 30–50 years, with most cases being mild to moderate in severity. Acneiform eruptions most frequently involved the face (89%), followed by the back (33%) and chest (27%). Lesion characteristics were documented in 159 patients; papules (82%), pustules (52%), and comedones (42%) were the most frequently reported. In contrast, nodules (19%) and cysts (18%) – features associated with more severe disease – were less commonly observed. Among the 213 patients with available time-to-onset data, the median time to acne onset following JAK inhibitor initiation was 47 days (IQR: 28–98 days). Patients with a previous history of acne vulgaris were significantly more likely to develop severe drug-induced acne (p<0.0001). Although corticosteroids are known to contribute to acne, our data did not demonstrate an association between concomitant steroid use and increased acne severity. There was also no difference in time to onset or resolution of acne between the steroid-treated and non-steroid treated groups. A third of patients reported a negative impact on psychosocial well-being, and 40% required pharmacological intervention. Topical therapies were required for 106 patients (39%), with 52 (49%) showing acne improvement or resolution. Systemic oral agents were required for 38 patients (14%), including 25 patients who did not respond or had a partial response to topical therapies. Antibiotics were prescribed to 29 patients (most commonly from the tetracycline class), leading to acne improvement or resolution in 14 patients (48%). Oral isotretinoin was required for 8 patients (3%) and was effective in all but one patient. Eighteen percent of patients who developed acne (2.2% of total cohort) required a JAK inhibitor dose reduction or discontinuation, although most did not have severe disease.

Conclusion

This study is the first to characterise this adverse event in JAK inhibitor-treated patients with IBD and presents the largest cohort of JAK inhibitor-induced acne cases to date across all immune-mediated diseases. JAK inhibitor-induced acne is a common adverse effect resulting in significant psychological burden. Early identification, proactive counselling, and timely interventions, such as dose reduction or referral to dermatology, are crucial in managing this side effect.

Introduction

Interleukin (IL) inhibitors are monoclonal antibodies that have been shown to be effective in inducing and maintaining remission in moderate to severe ulcerative colitis (UC).
Ustekinumab (UST) was approved in the EU for the treatment of UC in 2019 and binds specifically to the p40 protein subunit of IL-12 and IL-23. Mirikizumab (MIRI) was approved 4 years later and selectively binds to the p19 subunit of the IL-23 cytokine. By binding to the IL subunits, the interaction with the IL-23 receptor is inhibited.
In this study, we compared the response rate to induction therapy with UST and MIRI in patients with moderately to severe UC.

Aims & Methods

All patients with active UC who began induction therapy with UST or MIRI at our outpatient clinic between 2019 and 2024 were analyzed retrospectively with a follow-up period until April 2025. Patients who received the IL-23 inhibitor due to a disease other than UC or following a prednisolone therapy exceeding 20 mg and patients with pouchitis were excluded from the study.
We determined the response to IL-23 therapy 8 to 24 weeks after the start of treatment and documented this either as clinical remission (Mayo-Score ≤1), improvement (Mayo-Score reduction by at least 3 points), inadequate response (Mayo-Score reduction between 0 and 2) or no response (lack of benefit, switch to another medical class or colectomy).
We examined the levels of calprotectin in the stool 0 to 24 weeks before the start of IL-23 therapy up to 24 weeks after initial administration.
Our study included 40 patients treated with UST and 23 patients treated with MIRI, in the latter group 26% have previously been treated with UST. Patients in both groups were similar in age (mean age, 47.75 vs. 44.59 y; P 0.28), gender, disease duration (mean duration, 11 vs. 9 y; P 0.32), and extent of disease (pancolitis, 40% vs. 48%).

Results

After completion of induction, 25% in the UST group and 57% in the MIRI group reached clinical remission. MIRI after UST achieved clinical remission in 67%. Improvement was shown in 20% vs. 30%, UST vs. MIRI. For UST, 5% were non-responder. For MIRI, no non-responder was noted. In general, the difference between the pre- and post-induction Mayo-Score is significantly higher for MIRI, indicating a better response to the newly started drug (mean Mayo-Score difference, UST vs. MIRI, 2.95 vs 4.5; P 0.0003)
The mean calprotectin level before treatment was not significantly different (mean calprotectin, UST vs. MIRI, 1652 vs. 2452 mg/kg; P 0.17). The post-treatment calprotectin level was significantly higher for UST vs. MIRI (mean calprotectin, 1092 vs. 278 mg/kg; P 0.0083).

Conclusion

Mirikizumab is an effective induction treatment for patients with active ulcerative colitis, including those who previously did not respond adequately to Ustekinumab therapy.