AbbVie IBD Portfolio: Durability Data Strengthen Access Case, But Structural Barriers Persist for Both Assets

AbbVie Presents Long-Term IBD Data for SKYRIZI and RINVOQ at UEGW 2026

AbbVie presented 20 new scientific abstracts from its Inflammatory Bowel Disease (IBD) portfolio at the 2026 United European Gastroenterology (UEG) Week. The data highlighted long-term clinical and endoscopic outcomes for SKYRIZI (risankizumab) and RINVOQ (upadacitinib) in moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) over approximately three to four years. Key findings included sustained clinical and endoscopic remission rates for risankizumab in UC (COMMAND study) and upadacitinib in CD (U-ENDURE study). Real-world data from the UPlift study also demonstrated upadacitinib's effectiveness in CD, with 70.2% achieving clinical response within 12 weeks. Additionally, new data on the investigational dual-targeting therapy ABBV-466 in moderate-to-severe CD were presented.

• The COMMAND open-label extension study demonstrated sustained clinical and endoscopic outcomes for risankizumab in moderately to severely active ulcerative colitis patients for up to three years. At Week 96, as-observed clinical remission rates ranged from 54.0% to 73.1%, and endoscopic remission rates were between 38.8% and 53.5% with 180mg, observed across both advanced therapy-naïve and advanced therapy-experienced patients. These findings reinforce risankizumab's long-term benefit in managing UC.
• The U-ENDURE as-observed analyses showed that upadacitinib maintained clinical and endoscopic outcomes in moderately to severely active Crohn's disease patients for approximately four years. At Week 144, clinical remission was achieved by 78.9% of patients on 15 mg and 86.6% on 30 mg. Endoscopic remission rates were 47.1% and 64.2% for the 15 mg and 30 mg groups, respectively, highlighting its durable efficacy.
• Interim results from the real-world UPlift study in moderate to severe Crohn's disease showed that 70.2% of evaluable patients (N=497) achieved clinical response with upadacitinib within 12 weeks, with a median time to first response of 13 days. A separate real-world claims analysis in UC or CD patients indicated that switching from a TNF inhibitor to upadacitinib led to lower rates of IBD-related hospitalizations (9.5% vs 16.3%) or surgery (6.9% vs 10.6%) over 12 months compared to cycling to another TNF inhibitor.
• New data from the Phase 2a TARGET-CD study evaluated ABBV-466, an investigational dual-targeting therapy combining risankizumab (IL-23 inhibitor) with trosunilimab (α4β7 inhibitor), in patients with moderate-to-severe Crohn's disease. The primary results and molecular profiling from this study were presented, showing that ABBV-466 led to endoscopic remission, suggesting a promising novel approach by inhibiting inflammatory signaling and limiting immune-cell trafficking to the gut.

Sustained Clinical and Endoscopic Outcomes for SKYRIZI and RINVOQ

Long-term durability of response remains a central challenge in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with published data highlighting meaningful differences across biologic classes. In anti-TNF-experienced CD patients, ustekinumab demonstrated a clinical remission rate of 54.9% at year 1, rising to 76.92% at year 4 and 100% at year 5, with an overall persistence rate of 86.76% and a mean treatment duration of 27.65 months. This compares favourably to anti-TNF persistence, which declined from 72.06% at year 1 to 30.88% at year 3, versus 93.2% and 86.1% for ustekinumab at the same time points. In anti-TNF-refractory CD, ustekinumab was also associated with higher clinical remission (54.4% vs 38.3%) and treatment persistence (71.5% vs 49.7%) compared to vedolizumab at week 48, with particularly strong remission rates in patients with ileal location (OR 3.49) and penetrating behaviour (OR 6.58).

In UC, real-world data from the prospective RUN-UC study demonstrated that ustekinumab achieved 12-month treatment persistence of 93.9%, compared to 87.0% for vedolizumab and 75.0% for anti-TNF agents, a difference that was statistically significant (p < 0.001). However, propensity score-weighted clinical remission rates at month 12 were not significantly different across the three classes (ustekinumab 26.9%, anti-TNF 34.7%, vedolizumab 40.9%; p = 0.063). A separate meta-analysis in biologic-naive UC patients with long-term follow-up found that vedolizumab was associated with significantly greater treatment persistence than infliximab at 12, 24, 36, and 48 months, higher rates of clinical and endoscopic remission at 12 months, lower hospitalization rates at 12 and 36 months, and a lower incidence of serious adverse events, though no significant difference in persistence was observed at 60 months.

Therapeutic drug monitoring (TDM) data further inform long-term durability considerations. In IBD patients on adalimumab maintenance who experienced secondary loss of response despite therapeutic trough levels (>4.9 μg/mL), switching to a different biologic class was markedly superior to dose optimization: at 24 months, only 14.8% of patients in the swap group discontinued treatment versus 59.6% in the optimization group (P < 0.001), with a median time without discontinuation exceeding 24 months in the swap group compared to 13.3 months in the optimization group. A 2024 clinical practice guideline based on a meta-analysis of 10 trials (2,383 participants) issued a weak recommendation in favour of proactive TDM for intravenous infliximab during maintenance, while recommending against proactive TDM for adalimumab and other biologics during maintenance or at induction, underscoring that the evidence base for optimising long-term durability through proactive monitoring remains drug-specific and evolving.

RINVOQ's Real-World Impact: Comparing Treatment Strategies in IBD

In Crohn's disease, head-to-head comparisons between second-line biologics have demonstrated meaningful efficacy differences. A prospective registry study comparing vedolizumab and ustekinumab in anti-TNF-experienced CD patients found that, after adjusting for confounders, ustekinumab-treated patients were significantly more likely to achieve corticosteroid-free clinical remission (OR: 2.58, 95% CI: 1.36–4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10–4.96, P = 0.027), and combined corticosteroid-free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23–6.09, P = 0.014) at 52 weeks, while safety outcomes — including infections, adverse events, and hospitalisations — were comparable between the two groups. In pediatric CD, a single open-label multicenter RCT comparing first-line infliximab (FL-IFX) to conventional treatment in 100 newly diagnosed children with moderate-to-severe disease showed that clinical remission was achieved by 59% (24/41) in the FL-IFX group versus 34% (15/44) in the conventional-treatment group (RR 1.72, 95% CI 1.06–2.79; low certainty evidence), and endoscopic remission by 59% (16/27) versus 17% (5/30), respectively (RR 3.56, 95% CI 1.51–8.39; low certainty evidence), though the trial carried an overall high risk of bias. The EXTEND trial further demonstrated that continuous adalimumab maintenance following induction produced mucosal healing rates of 24% versus 0% for placebo at week 52 (P < .001), along with superior clinical remission rates at both weeks 12 (47% vs 28%; P = .021) and 52 (33% vs 9%; P = .001).

In ulcerative colitis, a systematic review with network meta-analysis comparing biologic therapies in moderately-to-severely active UC found that all biologics were more effective than placebo for inducing clinical response, clinical remission, and mucosal healing in anti-TNF-naïve patients. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (OR 2.19, 95% CrI: 1.35–3.55), clinical remission (OR 2.81, 95% CrI: 1.49–5.49), and mucosal healing (OR 2.23, 95% CrI: 1.21–4.14) during induction. In the maintenance setting, vedolizumab showed significantly superior durable clinical response compared to infliximab (OR 3.18, 95% CrI: 1.14–9.20), golimumab (OR 2.33, 95% CrI: 1.04–5.41), and adalimumab (OR 3.96, 95% CrI: 1.67–9.84). In anti-TNF-experienced UC patients, vedolizumab also demonstrated significantly improved mucosal healing versus adalimumab during maintenance (OR 6.72, 95% CrI: 1.36–41.0). Tofacitinib, an oral JAK inhibitor, has been approved for moderate-to-severe UC, with additional selective JAK-1 inhibitors — including filgotinib and upadacitinib — having shown positive results in phase II studies and advancing into phase III development programs.

Regarding cardiovascular safety of JAK inhibitors specifically in IBD, a systematic review and network meta-analysis of 26 trials involving 10,537 IBD patients found no significantly increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), or cardiovascular events (CVE) associated with JAK inhibitors overall. However, when dose was considered, tofacitinib 5 mg BID showed a trend toward increased MACE risk (OR = 1.05, 95% CI: 0.23–4.82) and upadacitinib 30 mg QD showed a trend toward increased VTE (OR = 1.36, 95% CI: 0.23–8.03) and CVE risk (OR = 1.08, 95% CI: 0.24–4.85). Notably, deucravacitinib ranked lowest for all cardiovascular risks and significantly decreased the risks of VTE (OR = 0.03, 95% CI: 0.00–0.87) and CVE (OR = 0.03, 95% CI: 0.00–0.87) compared with placebo. Conversely, blockade of IL-17A with secukinumab proved ineffective in CD, with a <0.1% probability of reducing CDAI by ≥50 points more than placebo, and was associated with higher rates of adverse events — including 20 infections on secukinumab versus none on placebo — underscoring that not all investigational mechanisms translate to clinical benefit across IBD indications.

Exploring Novel Dual-Targeting Therapy ABBV-466 in Crohn's Disease

The TL1A–DR3 axis has emerged as one of the most compelling dual-pathway targets in inflammatory bowel disease. TL1A (encoded by TNFSF15) signals through death receptor 3 on effector T cells, innate lymphoid cells, and intestinal myofibroblasts, simultaneously driving chronic mucosal inflammation — via enhancement of Th1 and Th17 effector functions — and tissue fibrosis through direct activation of fibroblasts and extracellular matrix deposition. Three anti-TL1A monoclonal antibodies — tulisokibart, afimkibart, and duvakitug — have advanced to Phase 3 trials, supported by Phase 2 clinical remission rates of 26%–48% in ulcerative colitis (placebo-adjusted differences of 15–26 percentage points) and endoscopic response rates of 26%–48% in Crohn's disease, alongside favorable safety profiles. A systematic review and meta-analysis further quantified the pooled clinical response rate at 67% in UC and 58% in CD, with an odds ratio for clinical remission of 3.75 (95% CI 2.04–6.89). Mucosal transcriptomic and serum proteomic analyses from Phase 2 trials, including DDW 2026 readouts from ARTEMIS-UC and TUSCANY-2, provided the first human-tissue confirmation of class antifibrotic activity through suppression of Th17, myeloid, and extracellular matrix pathways.

Beyond the lead anti-TL1A antibodies, the pipeline has expanded to at least 19 development programs targeting this mechanism. These include extended half-life antibodies (XmAb942, SPY002, and BCD-261), bispecific agents combining TL1A blockade with IL-23 or α4β7 inhibition (RO7837195, XmAb412, LQ080, and ALX001), a first-in-class oral anti-TL1A nanobody, and a first-in-class DR3 receptor antagonist, SL-325. TNFSF15 risk-variant companion diagnostics are also advancing, with their incremental utility to be definitively tested in Phase 3. Genetic data reinforce the mechanistic rationale: TNFSF15 risk haplotypes increase TL1A protein expression in response to FcγR stimulation, and the TL1A −358C/C genotype has been identified as an independent risk factor for surgery in Crohn's disease patients on anti-TNF therapy (hazard ratio 4.67; 95% CI 1.39–22.1; P = 0.025).

Separately, PANoptosis — a coordinated inflammatory cell death program integrating apoptosis, necroptosis, and pyroptosis — has been identified as an emerging therapeutic target in IBD. Key molecular regulators include the ZBP1–ADAR1 axis and RIPK1, with preclinical data suggesting that targeting PANoptotic regulators can restore intestinal barrier integrity. However, clinical translation has proven challenging: RIPK1 inhibitors such as GSK2982772 have failed to meet primary endpoints in Phase 2 trials, and IL-1/IL-18 targeting via anakinra has yielded disappointing clinical results in IBD, indicating that successful intervention in this pathway will likely require combination approaches or PANoptosome-specific modulators rather than single-pathway inhibition.

Sustaining IBD Remission: Long-Term Data and Next-Gen Strategies

The latest data from AbbVie's IBD portfolio at UEG Week paints a compelling picture of sustained efficacy and strategic foresight in a rapidly evolving therapeutic area. For established therapies like risankizumab and upadacitinib, the presentation of long-term clinical and endoscopic outcomes, spanning three to four years, is crucial. In the "treat-to-target" era, achieving and maintaining deep remission, including mucosal healing, is paramount for altering the natural history of Crohn's disease and ulcerative colitis. The evidence for risankizumab's durable clinical and endoscopic remission, alongside its corticosteroid-sparing effects, reinforces its value, particularly in patients with small bowel involvement or those refractory to other biologics.

Upadacitinib's profile is further enhanced by data demonstrating rapid symptomatic relief within the first week, significant improvements in quality of life and work productivity, and a notable reduction in hospitalization rates. These real-world insights, especially in highly treatment-refractory populations, underscore its potential as a comprehensive and impactful oral option. However, as a JAK inhibitor, upadacitinib's long-term safety profile, including risks of serious infections, herpes zoster, and other adverse events, remains a critical consideration for clinicians and patients. The concept of a 'positive switch' to biologics for patients maintaining remission but concerned about long-term JAK inhibitor risks highlights the ongoing need for individualized treatment decisions.

Looking ahead, the introduction of investigational dual-targeting therapy ABBV-466 signals a proactive approach to addressing the current "therapeutic ceiling" in IBD. While dual-targeted therapies hold promise for overcoming the extensive redundant inflammatory networks, their efficacy and safety data are still emerging. This strategic move suggests a commitment to innovation beyond existing mechanisms, potentially offering new hope for patients who do not adequately respond to current treatments. The future of IBD management will likely involve a more personalized, mechanism-based approach, leveraging both established and novel therapies to optimize long-term outcomes.