Marla Dubinsky, MD, is chief of the division of pediatric gastroenterology and nutrition and co-director of the Susan and Leonard Feinstein IBD Clinical Center, Mount Sinai Kravis Children's Hospital, Icahn School of Medicine.

Marla Dubinsky, MD

The Drug Holiday Dilemma in IBD — and How SC Infliximab Changes It

Treatment interruptions with anti-TNFs are common in clinical practice, driven by loss of response, safety concerns, pregnancy, or patient preference. Historically, reintroducing the drug intravenously has carried meaningful risk.

However, new post hoc data from the phase 3 LIBERTY trials suggest that subcutaneous (SC) infliximab may offer a safer, more durable path back to disease control for patients with 

Crohn's disease (CD) or ulcerative colitis (UC)

 following a drug holiday. The analysis was presented by Marla Dubinsky, MD, a gastroenterologist and professor of medicine at the Icahn School of Medicine at Mount Sinai, at Digestive Disease Week (DDW) 2026 in Chicago, IL.

"Historically, about 50% of patients are off anti-TNF therapy over the first 2 to 3 years," Dubinsky told 

. "Before we understood drug levels and antibodies, we just waited for people to lose response and then moved on."Before we understood drug levels, safety, antibodies, there were quite a number of patients who were stopping it, predominantly for loss of response, with a large number of them associated with anti drug antibodies because they were not proactively optimized. We just waited for people to lose response, got a drug level and said ‘You've now got antibodies, I have to move on.’”

The LIBERTY-CD and LIBERTY-UC trials randomly assigned patients who responded to IV infliximab induction to either SC infliximab 120 mg or placebo every other week through week 54. Patients in the placebo arm who experienced disease recurrence after a minimum 16-week drug holiday were eligible to receive SC infliximab 240 mg, double the approved maintenance dose, as a form of reintroduction.

The present post hoc analysis evaluated 51 CD and 77 UC patients from the placebo arms, assessing clinical, biochemical, endoscopic, and pharmacokinetic outcomes through week 102.

Early clinical responses emerged within 8 weeks of SC infliximab initiation and were sustained throughout the study period, with partial clinical response rates of 92.3% in CD and 96.6% in UC at treatment end. Fecal calprotectin remission was achieved in 61.1% of CD patients and 65.2% of UC patients, with endoscopic response rates of 64.0% and 68.8%, respectively. Additionally, treatment persistence through week 102 was 72.3% in CD and 61.9% in UC.

Dubinsky highlighted the parallel between clinical recapture and pharmacokinetic recovery as a key finding. Serum infliximab levels rose markedly after SC reintroduction and remained stable, a pattern that tracked directly with clinical response.

“You see this parallel where you get this recapturing in 8 weeks, and when you look at the trough level, you then see you've recaptured the trough level that you stay at throughout that period of you now being in the 240 arm,” she said. “I think the fact that you see that association of the PK coming back after no drug level, or a honeymoon during that period, and you see that clinical response parallel the recapture of the trough level, or that consistent, sustained drug level that we're used to, really tells you that you recapture because you're able to bring back the drug concentration that's associated with response.”

Dubinsky additionally highlighted immunogenicity findings as among the most clinically significant data from her research. Reintroduction of IV infliximab after a drug holiday carries well-documented risk of infusion reactions, driven by a surge in anti-drug antibodies (ADAs) upon re-exposure. SC reintroduction appeared to sidestep this problem. Despite high ADA rates at the time of SC reintroduction, antibody status had minimal impact on outcomes, with approximately three quarters of patients maintaining treatment persistence regardless of ADA status.

Dubinsky noted that SC infliximab 240 mg is not currently FDA-approved for this indication in the US, but expressed hope that publication of these data would support conversations with payers and health authorities about its clinical utility.

Editor's note: Dubinsky reports relevant disclosures with AbbVie, Abivax, Astra Zeneca, BMS, Celltrion, Eli Lilly, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Roche, Sanofi, Spyre, Takeda, and others.

Dubinsky MC, Sands BE, Abraham BP, et al. Recapturing Disease Control With Subcutaneous Infliximab After a Drug Holiday Following Intravenous Infliximab Induction: A Post Hoc Analysis of LIBERTY-CD and -UC Studies. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Rubin DT. Restarting Biologic Agents After a Drug Holiday. 

Videos

Marla Dubinsky, MD, explains LIBERTY post hoc data showing SC infliximab 240 mg recaptured clinical response within 8 weeks in CD and UC patients following a drug holiday.

Subcutaneous Infliximab Recaptures Disease Control After Treatment Interruption in IBD

The recent US Food and Drug Administration approval of Lilly’s mirikizumab (Omvoh) for the treatment of moderately to severely active Crohn’s disease (CD) expands the interleukin(IL)-23p19 antagonist’s impact on 

 care, building upon its 2023 approval for 

The January 15, 2025, decision was based on positive results from the phase 3 VIVID-1 study in adults with moderately to severely active CD who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, and/or biologics. Both primary endpoints were achieved, with 53% of patients treated with mirikizumab achieving clinical remission at 1 year versus 36% on placebo (

<.001) and 46% of patients treated with mirikizumab experiencing visible healing of the intestinal lining at 1 year versus 23% on placebo (

For additional insight into the need for effective therapies in CD and the significance of now having mirikizumab as a treatment option, the editorial team of 

 spoke with Marla Dubinsky, MD, chief of the division of pediatric gastroenterology and nutrition and co-director of the Susan and Leonard Feinstein IBD Clinical Center, Mount Sinai Kravis Children's Hospital, Icahn School of Medicine.

 Can you explain what CD treatment has historically looked like and what unmet needs exist for effective therapies?

The introduction of anti-TNF therapies in the late 1990s revolutionized treatment. We quickly learned that TNF was not the right target for all patients. At first, we believed all roads led to TNF no matter the disease state or pathway, so we were okay with going very downstream.

Then, we realized there are primary nonresponders to TNF for whom that is not the right target. We also learned that over time, a significant amount of patients were losing response to anti-TNF, so the durability was in question.

This was more at the beginning when we were using episodically and there were anti-drug antibodies. The dosing on label was based on whether someone felt better. For UC, there was always an endoscopic component to outcomes for clinical trials. In Crohn’s disease, we started with “Do you feel better over the last 7 days?”

We know that for patients who don't have inflammation but have more sort of disorders of gut-brain interaction, maybe an IBS overlay, when you answer the CDAI, it can overlap significantly with some of our patients who also have these functional symptoms or patient-reported outcomes.

In the SONIC trial, about 50% of patients who said clinically they felt great on either infliximab monotherapy or infliximab plus a thiopurine or a thiopurine alone and met the CDAI score change of less than 150 had ulcerations on their colonoscopy that we were blinded to. The other 50% said they didn’t feel well. They had a CDAI score that met that disease activity, their scope was normal.

That disconnect between objective and subjective is so paramount to us understanding why, despite having incredible treatments and using them early, we still had a significant amount of patients going to the operating room. A lot of that was because we were following symptoms only. We were not using the TNFs correctly from a dosing standpoint, because we started off with episodic infliximab and the exposure response was so far off.

 What are some of the issues with anti-TNFs that merited the clinical development of IL-23 antagonists? How does the mirikizumab approval build upon this?

TNF is an incredible target, and when anti-TNF is used correctly and used early, there’s not much else you need. But there’s a group of patients where we just can't get enough of the dosing. They need more than what's on label, even if we use it escalated or optimized. TNF is not their primary cytokine, and by waiting far down the line to TNF, we may be missing an upstream opportunity to get better disease control and not wait for TNF to overwhelm the system.

We also had some realizations about safety. When I tell my patients there is a Black Box warning around TNFs, particularly when I talk about pregnancy or pediatric utilization, there's a fear about the safety hits it comes with. We know that, but to be fair, it is probably the class with the highest denominator on the planet compared to all of our other drugs, where although there are warnings around infection and lymphoma risk and other serious warnings, it is still the most utilized target we have.

That's all a lot of work and a lot of gymnastics, so we would like an easier button. When risankizumab first came out and endoscopy was part of the primary outcome, we learned that IL-23 works very well in naive patients, the same as what you see with mirikizumab. We also noted that there is no warning, there are very good pharmacokinetics, and these drugs appear to be extremely durable. You don't need to use a thiopurine with it, so you're not increasing the risk.

I think there's always a need for innovation. There is a need to understand the overlap between skin conditions and rheumatic conditions and GI. We tend to follow the lead like we did with risankizumab from psoriasis data. Interestingly, mirikizumab was only tested in the IBD space. The goal was not to first get it approved in a joint or skin condition, but instead to go straight to IBD, and it has had its approval for ulcerative colitis for a while now. I think all of that results in patients and physicians and any stakeholder wanting a drug that they can have confidence in that has proof of endoscopic remission and healing.

We know with mirikizumab, for example, that we had a significant amount of patients who not only met clinical deep remission versus placebo, but also met the mucosal aspect with healing of the intestinal lining being double the percentage that we saw with placebo.

Overall, we are entering an era where confidence and safety matters. I think mirikizumab represents a positive and forward movement in this class, where we are able to help patients feel better, both with the healing of their lining and also from an emotional perspective. We don't talk enough about the importance of urgency or fatigue. The fact that we've advanced our therapies to look at the whole person is really the new era of looking at drug efficacy, value, and validity.

Brooks A. FDA Approves Mirikizumab (Omvoh) for Crohn’s Disease. 

. January 15, 2025. Accessed January 17, 2025. 

https://www.hcplive.com/view/fda-approves-mirikizumab-omvoh-for-crohn-disease

Articles

Lilly's mirikizumab (Omvoh) has been approved by the FDA for treating moderately to severely active Crohn’s disease, following its prior approval for ulcerative colitis. This decision was based on the VIVID-1 study, which demonstrated significant clinical remission and intestinal healing in patients. Historically, anti-TNF therapies have been pivotal but have limitations, including nonresponse and safety concerns. Mirikizumab, an IL-23 antagonist, offers a promising alternative with favorable safety and efficacy profiles, marking a significant advancement in inflammatory bowel disease management.

Dubinsky describes the evolution from anti-TNF therapies to IL-23 antagonists and the significance of mirikizumab’s approval for Crohn’s disease.

Marla Dubinsky, MD: Ushering In a New Era of Crohn’s Disease Treatment with Mirikizumab

Experts in gastroenterology discuss treatment selection in special situations of CD, such as age, women considering pregnancy, extra-intestinal manifestations.

Selecting CD Treatment in Special Scenarios

This is a video synopsis/summary of a panel discussion involving Marla Dubinsky, MD; David Rubin, MD; Miguel Regueiro, MD; Remo Panaccione, MD, FRCPC; and Sara Horst, MD, MPH.

The discussion revolves around advanced therapies for Crohn's disease, focusing on specific scenarios and the choice of treatments. The participants discuss their preferences based on various patient characteristics and conditions.

The conversation begins with considerations for patients previously exposed to anti-TNF (tumor necrosis factor) therapies. Natalizumab is deemed less effective in this population, and risankizumab is suggested as a preferable option over upadacitinib due to similar data outcomes. The need for speed in specific cases, such as those with extra-intestinal manifestations, is highlighted, making upadacitinib an attractive choice.

The panel discusses the importance of personalized medicine, considering factors like inflammatory joint problems, spondyloarthropathy, or other manifestations. Choices are tailored to individual patient profiles, with IL (interleukin)-23-based strategies favored for certain scenarios.

Pregnant women are advised on the importance of disease control, with emphasis on the safety of IL-23 and IL-12/23, alongside traditional anti-TNF options. The potential use of JAK (Janus kinase) inhibitors for quick induction of deeper remission is acknowledged.

The safety profile of JAK inhibitors is addressed, dispelling misconceptions and encouraging broader utilization in IBD (inflammatory bowel disease) management. The discussion concludes with a rapid-fire round where each participant shares their first-line therapy preferences for specific patient scenarios.

In closing, the participants express hope for the future of Crohn's disease management, emphasizing the evolving landscape of precision medicine, advancements in fibrosis treatment, the paradigm shift in disease monitoring, and the promise of combination therapies. The concept of treating Crohn's disease earlier in its course is highlighted as a future goal, providing optimism for improved patient outcomes.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Experts in gastroenterology discuss treatment selection in special situations of CD, such as age, women considering pregnancy, and extra-intestinal manifestations.

Remo Panaccione, MD, FRCPC, provides an overview of the newest oral therapy approved for CD, upadacitinib.

Use of Upadacitinib in Treatment of CD

The discussion shifts to the newest drug for Crohn's disease, upadacitinib, a selective JAK (Janus kinase) 1 inhibitor. The speaker outlines the mechanism of upadacitinib, distinguishing it from other JAK inhibitors and emphasizing its selectivity for JAK1. The drug's impact on the JAK-STAT pathway and its role in modulating gene transcription for pro-inflammatory cytokines are discussed.

Upadacitinib is highlighted for its specificity in targeting JAK1 without significant effects on JAK2, which reduces the risk of off-target effects associated with myelofibrosis and erythropoiesis. The speaker explains that JAK inhibitors act as competitive agonists, binding to the intracellular side of the receptor and competing for STAT activation.

The drug's approval for Crohn's disease is discussed, with a comparison to another treatment mentioned earlier in the conversation. The speaker notes that the data for upadacitinib, an oral small molecule, aligns closely with the effects of the mentioned treatment, administered differently. The discussion emphasizes the drug's effectiveness in achieving clinical and endoscopic remission, with particular attention to its rapid action, possibly quicker than other options.

The speaker shares personal experiences, mentioning that upadacitinib is used as a first-line therapy for Crohn's disease in Canada for about 15% of patients. The drug is frequently used clinical practice, attributed to its quick efficacy and ability to rescue a significant number of patients. The convenience of an oral small molecule is underlined, especially in gastrointestinal diseases, addressing pharmacodynamic challenges associated with monoclonal antibodies in inflamed guts.

In summary, upadacitinib emerges as a remarkable and versatile drug, praised for its selectivity, efficacy, and oral administration. The speaker's experiences and the drug's potential as a first-line therapy contribute to its significance in the evolving landscape of Crohn's disease treatment.