Small Molecules, Combination Strategies & Emerging Therapies
Module Overview
JAK inhibitors (tofacitinib, upadacitinib, filgotinib), S1P receptor modulators (ozanimod, etrasimod), and the pipeline of emerging therapies. Combination and sequencing strategies.
Benchmark Source: Cleveland Clinic Pharmacotherapy + ECCO Advanced Therapy Modules
Learning Objectives
Prescribe JAK inhibitors with appropriate safety monitoring
Explain the mechanism and positioning of S1P modulators
Design a treatment sequencing strategy after biologic failure
Evaluate pipeline therapies and interpret phase 2/3 trial data
Teaching Sessions
JAK Inhibitors: Tofacitinib, Upadacitinib, Filgotinib
A 2.5-hour deep dive on Janus kinase inhibitors in IBD: pharmacology, pan-JAK vs selective JAK1 profiles, pivotal trial evidence (OCTAVE, U-ACHIEVE, U-EXCEL, SELECTION), ORAL Surveillance safety signals, and Saudi MOH positioning including age and cardiovascular risk considerations.
1JAK-STAT signaling and drug pharmacology (30 min)
JAK-STAT pathway transmits signals from ~50 cytokines via four JAK kinases (JAK1, JAK2, JAK3, TYK2) and STAT transcription factors. In IBD, JAK1 mediates signaling for key inflammatory cytokines IL-6, IFN-γ, and IL-2 family. Tofacitinib is a pan-JAK1/2/3 inhibitor; upadacitinib and filgotinib are selective JAK1 inhibitors (theoretically lower off-target effects on erythropoiesis and NK cells). Oral bioavailability, rapid tissue distribution, short half-life allow daily or twice-daily dosing. Tofacitinib: 10 mg BID induction × 8 weeks then 5 mg BID maintenance (escalate to 10 mg BID for inadequate response). Upadacitinib: 45 mg QD induction × 8 weeks then 15 or 30 mg QD. Filgotinib: 200 mg QD.
Small molecules have the huge advantage of rapid onset (days to 2 weeks) and oral dosing — reserve for patients needing fast relief or who cannot tolerate injections.
- JAK1 is the key target for IBD-relevant cytokines
- Tofacitinib pan-JAK; upadacitinib/filgotinib selective JAK1
- Rapid onset: clinical response within days to 2 weeks
- Oral dosing, short half-life
- Withdrawal of drug reverses effect within days — useful for pre-op
2Tofacitinib evidence: OCTAVE induction and maintenance (30 min)
OCTAVE Induction 1 and 2 (NEJM 2017): tofacitinib 10 mg BID × 8 weeks induced remission in ~18% vs 8% placebo in moderate-severe UC. OCTAVE Sustain: 5 mg BID or 10 mg BID maintenance × 52 weeks; remission rates 34% (5 mg) and 41% (10 mg) vs 11% placebo. Rapid onset: stool frequency improvement within 3 days. Effective in anti-TNF-exposed patients (about 50% of study population). OCTAVE Open long-term extension: sustained efficacy over 4+ years for continued responders. No efficacy in CD (RCT failed); not approved for CD.
Tofacitinib is UC-only — the CD program failed. Do NOT use for CD even if patient responded to other JAK inhibitors in trials.
- OCTAVE Induction: 18% vs 8% remission at week 8
- OCTAVE Sustain: 41% (10 mg) vs 11% placebo at 52 weeks
- Stool frequency improves within 3 days
- Effective in anti-TNF failures
- Not approved for CD (CD trial failed)
3Upadacitinib evidence: U-ACHIEVE, U-EXCEL, U-EXCEED (30 min)
U-ACHIEVE (UC, 2022): induction remission 26% vs 5% placebo at week 8; maintenance U-ACHIEVE Maint: 42% (15 mg) and 52% (30 mg) vs 12% placebo at week 52. U-EXCEL and U-EXCEED (CD, 2023): induction remission 35% vs 4% placebo at week 12 (U-EXCEED in biologic-inadequate response); maintenance U-ENDURE: 37% (15 mg) and 48% (30 mg) vs 14% placebo at week 52. Approved for both UC and CD. Endoscopic remission rates 18-40% across trials.
Upadacitinib has approved CD data unlike tofacitinib — it is the JAK of choice for CD patients who need oral therapy or have failed multiple biologics.
- U-ACHIEVE: 26% vs 5% UC induction remission
- U-ENDURE CD maintenance: 48% on 30 mg vs 14% placebo
- Endoscopic remission 18-40%
- Approved for both UC and CD
- Rapid onset similar to tofacitinib
4ORAL Surveillance safety and boxed warnings (30 min)
ORAL Surveillance (tofacitinib in RA, 2022) compared tofacitinib to TNF inhibitors in patients ≥50 with ≥1 CV risk factor. Found increased MACE (HR 1.33), malignancy (HR 1.48), and VTE (HR 2.2 for PE). FDA applied boxed warning class-wide to all JAK inhibitors. In IBD: avoid in patients >65, known CV disease or multiple CV risk factors, current/prior malignancy (within 5 years), prior VTE or high VTE risk, active smokers >20 pack-years. In safe patients, JAK inhibitors are reasonable; in higher-risk patients, consider anti-TNF or vedolizumab. Lab monitoring: CBC (lymphopenia, neutropenia), lipids (LDL rise), LFTs, creatinine, HBV/HCV/TB screening pre-treatment.
Before starting any JAK in Saudi Arabia, document age, BMI, smoking status, prior malignancy, CV history, and VTE risk — this is essential medicolegal documentation.
- ORAL Surveillance: MACE HR 1.33, malignancy HR 1.48, VTE HR 2.2
- FDA boxed warning class-wide for all JAK inhibitors
- Avoid in >65, CV disease, malignancy, VTE history, heavy smokers
- Monitor CBC, lipids, LFTs, creatinine
- Pre-treatment TB/HBV/HCV screening mandatory
5Positioning, Saudi MOH approval, and patient counseling (30 min)
Ideal JAK candidate: moderate-severe UC (tofacitinib or upadacitinib) or CD (upadacitinib) patient <60, no CV disease, no malignancy history, prior biologic failure (especially anti-TNF), patient preference for oral therapy, pregnancy unlikely in next 1 year (JAKs contraindicated in pregnancy). Saudi MOH approval requires: moderate-severe endoscopic disease, prior biologic failure or intolerance, patient education, and documented safety screening. Counsel patients: rapid onset as benefit, contraindications, shingles vaccine (Shingrix non-live recommended before initiation), avoid live vaccines during therapy, plan pregnancy carefully (washout 1 month), report infection promptly.
Shingrix (non-live recombinant zoster vaccine) is recommended BEFORE JAK initiation in all patients >50 and reasonable in younger patients — JAK inhibitors increase herpes zoster risk 2-3×.
- Ideal JAK candidate: <60, low CV risk, prior biologic failure
- Saudi MOH approval: endoscopic evidence + prior biologic failure
- Shingrix vaccination before initiation
- Avoid pregnancy (contraindicated); washout 1 month
- Counsel on infection and malignancy risk
- JAK inhibitors are oral, rapid-onset, and reversible — ideal for patients needing fast relief or avoiding injections
- Tofacitinib is UC-only; upadacitinib approved for both UC and CD
- ORAL Surveillance requires caution in >65, CV disease, malignancy, and VTE history
- Shingrix vaccine before initiation and annual TB/HBV/HCV monitoring
- Saudi MOH approval typically requires prior biologic failure + endoscopic moderate-severe disease
S1P Receptor Modulators: Ozanimod and Etrasimod
A 1.5-hour overview of sphingosine-1-phosphate receptor modulators in UC: mechanism, TRUE NORTH and ELEVATE evidence, cardiac and hepatic monitoring protocols, and positioning alongside JAK inhibitors.
1S1P receptor biology and mechanism (30 min)
Sphingosine-1-phosphate (S1P) is a bioactive lipid that binds five GPCR receptors (S1P1-5). Lymphocytes use S1P1 gradient to egress from lymph nodes. S1P receptor modulators (ozanimod, etrasimod) cause functional antagonism of S1P1 on lymphocytes, sequestering them in lymph nodes and reducing circulating lymphocytes and gut lymphocyte trafficking. Ozanimod selective for S1P1 and S1P5; etrasimod selective for S1P1, S1P4, and S1P5. Both administered orally once daily. Rapid onset of lymphocyte reduction (days) and clinical effect within 4-8 weeks.
S1P modulators require dose titration over 1 week (ozanimod) or 2 weeks to minimize cardiac and lymphopenic effects — skipping titration is dangerous.
- S1P1 receptor sequesters lymphocytes in lymph nodes
- Reduces lymphocyte trafficking to gut mucosa
- Oral once-daily dosing
- Dose titration required over 7-14 days
- Onset 4-8 weeks for clinical response
2Evidence: TRUE NORTH and ELEVATE UC (30 min)
TRUE NORTH (ozanimod, NEJM 2021): moderate-severe UC, induction remission 18.4% vs 6.0% placebo at week 10; maintenance 37.0% vs 18.5% placebo at week 52. ELEVATE UC 52 and UC 12 (etrasimod, Lancet 2023): induction remission 27% vs 7% placebo at week 12; maintenance 32% vs 7% at week 52. Both effective in biologic-naive and biologic-experienced UC. CD trials ongoing (CULTIVATE).
S1P modulators are UC-only approved — CD studies ongoing. Choose by profile: ozanimod available longer in Saudi market, etrasimod has shorter titration.
- TRUE NORTH: 18.4% vs 6% induction, 37% vs 18.5% maintenance
- ELEVATE UC 12: 27% vs 7% induction
- Effective in biologic-naive and biologic-experienced UC
- CD trials (CULTIVATE) ongoing
- Sustained long-term response in open-label extensions
3Monitoring and safety: cardiac, hepatic, ophthalmic (30 min)
Pre-treatment: ECG (baseline HR, PR interval), LFTs, CBC, ophthalmology exam if diabetic or uveitis history, varicella/zoster immunity, HBV screening. First dose: observe for 6 hours if ECG abnormalities OR heart rate <55 OR PR >0.19 sec. Dose titration: ozanimod 0.23 mg days 1-4, 0.46 mg days 5-7, then 0.92 mg; etrasimod 2 mg daily (no titration needed). Contraindications: MI/unstable angina within 6 months, heart failure within 6 months, class III/IV HF, Mobitz II or 3rd-degree AV block, sinus node dysfunction without pacemaker, severe hepatic impairment. Monitor: LFTs q1-2 months × 6 months then periodically, CBC for lymphopenia, macular edema screening at 3-6 months especially in diabetics.
In Saudi Arabia where diabetes prevalence is high, ophthalmology baseline and 3-6 month re-check for macular edema is non-negotiable.
- Baseline ECG for all patients; observe first dose if abnormalities
- Dose titration over 7 days (ozanimod) or none (etrasimod)
- Contraindications: recent MI/HF, conduction disease
- LFT monitoring q1-2 months × 6 months
- Ophthalmology screening for macular edema, esp diabetics
- S1P modulators sequester lymphocytes in lymph nodes — oral, rapid-onset, UC-approved
- TRUE NORTH and ELEVATE UC established efficacy in moderate-severe UC
- Dose titration (ozanimod) and baseline ECG mandatory for all patients
- Monitor LFTs monthly × 6 months; ophthalmology screening in diabetics
- Not yet approved for CD — ozanimod CULTIVATE trial ongoing
Positioning and Sequencing Small Molecules After Biologic Failure
A 2-hour case-based discussion of how to position JAK and S1P modulators in the IBD treatment algorithm — when to choose oral small molecules, how to sequence after biologic failure, and patient-centered selection.
1Patient selection framework: oral vs parenteral (30 min)
Preferred oral candidates: injection-phobic, frequent travel, Hajj/Umrah pilgrimage logistics, young professional with busy schedule, pediatric-to-adult transition needing patient control. Preferred parenteral (biologic) candidates: pregnancy planning (most biologics better studied), elderly with CV risk, active malignancy history, severe heart failure, established latent TB awaiting treatment. Shared decision-making: discuss oral vs injected, frequency, blood monitoring, pregnancy plans, travel patterns, cost, and payer approval timelines.
Hajj and Umrah logistics are a real Saudi consideration — oral small molecules avoid the cold-chain and injection-site concerns during pilgrimage for eligible patients.
- Oral preferred: injection phobia, travel, Hajj/Umrah, pediatric transition
- Parenteral preferred: pregnancy, CV risk, malignancy history, latent TB
- Shared decision-making essential
- Consider payer approval timelines (MOH usually 2-4 weeks)
- Counsel on pregnancy contraindication for JAKs
2Sequencing after anti-TNF failure: algorithm (30 min)
After anti-TNF failure with confirmed antibody-mediated LOR: switch within class (different anti-TNF) reasonable, ~50% response. If mechanistic failure (adequate trough with disease): out-of-class — vedolizumab, ustekinumab, risankizumab (CD, SEQUENCE data), JAK inhibitors (tofacitinib UC, upadacitinib UC/CD), or S1P modulators (ozanimod/etrasimod UC). Sequential biologic exposure in IBD dilutes efficacy — each subsequent agent has lower remission rates. Therefore choose wisely early. If first biologic fails, consider oral small molecule as second line in UC before cycling through more biologics — rapid onset, different MOA, patient preference.
Do not cycle through 3 biologics before trying an oral small molecule in UC — the patient loses time and the drug response diminishes with each biologic exposure.
- Anti-TNF failure: within-class for AB-driven, out-of-class for mechanistic
- Oral small molecule is a reasonable 2nd-line option in UC
- Each sequential biologic has diminishing response
- Saudi payers increasingly approve small molecules as 2nd line
- Consider JAK early in young UC patients without CV risk
3Case discussions: 5 real Saudi scenarios (30 min)
Case 1: 25-year-old UC after IFX failure, wants to travel for Hajj — upadacitinib 45 mg QD with Shingrix pre-vaccination. Case 2: 62-year-old UC with prior MI — avoid JAK, use vedolizumab. Case 3: 28-year-old CD with perianal fistulae after 2 anti-TNFs and ustekinumab failure — upadacitinib 45 mg QD with careful monitoring. Case 4: 35-year-old UC, biologic-naive, requests oral option — etrasimod reasonable after insurance approval but prefer anti-TNF + AZA (SONIC UC-SUCCESS). Case 5: 19-year-old UC transitioning from pediatric care, severe activity — rapid induction with tofacitinib 10 mg BID while confirming safety workup.
Document "prior biologic failure" and "patient preference" in the chart for payer — this is the standard Saudi MOH approval pathway for small molecules.
- Young UC patients with Hajj plans: upadacitinib
- Elderly with CV risk: avoid JAK, use vedolizumab
- Refractory CD: upadacitinib 45 mg with monitoring
- Biologic-naive seeking oral: etrasimod reasonable
- Rapid induction needed: tofacitinib 10 mg BID
4De-escalation and exit strategies (30 min)
Once remission achieved: consider dose reduction (tofacitinib 10 → 5 mg BID, upadacitinib 45 → 15/30, ozanimod sustained at 0.92 mg). De-escalation within first year of remission has higher relapse risk; wait 12-24 months of sustained deep remission (endoscopic + biochemical). Check calprotectin before and after every dose reduction. Consider biologic maintenance if small molecule de-escalation fails. Pregnancy planning: washout 1 month for JAK (hard stop contraindication), 10 days for ozanimod, 14 days for etrasimod. Monitor for rebound post-discontinuation: schedule endoscopy 3 months after stopping.
Never de-escalate small molecules without a baseline endoscopy and calprotectin — rebound relapse is rapid and can be severe.
- Wait 12-24 months of deep remission before de-escalation
- Calprotectin before and after dose reduction
- Tofacitinib 10 → 5 mg BID; upadacitinib 45 → 15/30
- Pregnancy washout: JAK 1 month, S1P 10-14 days
- Schedule endoscopy 3 months post-discontinuation
- Oral small molecules ideal for injection-phobic, travelers, Hajj/Umrah pilgrims, and young professionals
- Consider JAK or S1P as 2nd-line in UC after anti-TNF failure rather than cycling biologics
- Avoid JAKs in elderly, CV disease, malignancy, and VTE history per ORAL Surveillance
- S1P modulators require ECG, LFTs, and ophthalmology baseline + ongoing monitoring
- Do not de-escalate without 12-24 months deep remission and objective confirmation
Pipeline Small Molecules and Emerging Oral Therapies
A 1.5-hour tour of the small-molecule pipeline in IBD: TYK2 inhibitors, selective integrin inhibitors, oral peptides, gut-restricted agents, and the outlook for the next 2-3 years.
1TYK2 inhibitors and selective JAK1 (30 min)
Deucravacitinib (approved for psoriasis) targets TYK2 pseudokinase domain allosterically, preserving JAK1/2/3 signaling and theoretically avoiding the ORAL Surveillance safety signals. IBD trials underway (DIVERSITY, LATTICE-UC). Abrocitinib and baricitinib being investigated in IBD. Selective JAK1: upadacitinib and filgotinib already established. Future: compound-specific selectivity profiles to improve benefit-risk ratio. Pipeline will continue to expand oral options over 2026-2028.
Track ClinicalTrials.gov for DIVERSITY and LATTICE-UC readouts — deucravacitinib may offer JAK-like efficacy without cardiovascular boxed warnings.
- Deucravacitinib: TYK2 allosteric inhibitor
- May avoid ORAL Surveillance safety signals
- DIVERSITY and LATTICE-UC trials ongoing
- Abrocitinib, baricitinib investigated
- Selective JAK pipeline expanding
2Oral α4β7 and gut-restricted agents (30 min)
AJM300 (carotegrast methyl) is an oral α4 integrin inhibitor approved in Japan for UC, with 8-week remission data. Gut-restricted agents (novel concept) maximize mucosal exposure while minimizing systemic effects. Morphogen pathway modulators and IL-22 agonists in early development. Oral peptide biologics under investigation (lower cost than injectable monoclonals). Microbiome-targeted small molecules (SER-287, fecal-derived live biotherapeutics) in trials.
Oral α4 integrin inhibitors may become a real alternative to vedolizumab SC — monitor Japanese and EU regulatory pathways for timing.
- AJM300: oral α4 inhibitor approved in Japan for UC
- Gut-restricted agents reduce systemic exposure
- Oral peptide biologics cheaper than monoclonals
- Microbiome-targeted small molecules in trials
- IL-22 agonists restoring epithelial barrier
3Research landscape and Saudi trial participation (30 min)
Saudi IBD centers (KFSHRC, KAMC, KSUMC, KAUH) are increasingly participating in global Phase 2 and 3 small-molecule trials. Saudi Gastroenterology Association supports site enrollment. Benefits: early patient access to novel therapies, academic publication, faculty development. Challenges: PDPL compliance, IRB timelines, MOH trial registration, patient consent in Arabic, ethnic-specific pharmacogenomics underrepresented in global databases. SGA advocacy for increased Saudi representation in trials.
Approach SGA research committee early for site feasibility — Saudi trial participation is growing and SGA supports sites through regulatory setup.
- Saudi centers participating in Phase 2/3 small-molecule trials
- SGA research committee supports site setup
- PDPL compliance and IRB timelines are key challenges
- Arabic patient consent materials needed
- Advocate for Saudi/Gulf ethnic representation in pharmacogenomics
- Deucravacitinib and TYK2 inhibitors may avoid ORAL Surveillance safety signals
- AJM300 (oral α4) already approved in Japan for UC
- Gut-restricted and oral peptide agents expanding the oral IBD toolbox
- Saudi IBD centers participating in global trials via SGA research committee
- Advocate for Gulf/Arab ethnic representation in pharmacogenomics and trial data
Refractory IBD: When Small Molecules and Biologics Both Fail
A 2-hour case-based session on the approach to truly refractory IBD after multiple biologic and small-molecule failures — reassessment, combination therapy, surgical consultation, and palliation.
1Reassessment of diagnosis and non-inflammatory factors (30 min)
Before declaring refractory IBD, question the diagnosis: could this be intestinal TB, Behçet, NSAID enteropathy, monogenic IBD (especially in early-onset <6 years), ICI colitis, segmental colitis associated with diverticulosis, or ischemic colitis? In Saudi Arabia, intestinal TB and Behçet are important mimics that require specific testing (QuantiFERON with TB PCR on tissue, ophthalmology and oral examination for Behçet). Consider genetic testing (IL-10R, XIAP, FOXP3) in early-onset or atypical cases. Confirm adherence, review for stricture-dominant disease (surgical), assess psychosocial stressors.
Consider monogenic IBD (IL-10R mutations especially) in any patient with very-early-onset disease (<6 years) or extreme refractoriness — molecular diagnosis changes treatment (HSCT).
- Question diagnosis: TB, Behçet, monogenic IBD, ICI colitis
- Saudi context: intestinal TB and Behçet are important mimics
- Genetic testing in very-early-onset or atypical disease
- Confirm adherence and exclude structural mimics
- Monogenic disease (IL-10R, XIAP) may be curable with HSCT
2Combination biologic and small molecule therapy (30 min)
Combination biologic therapy (e.g., vedolizumab + ustekinumab, IFX + vedolizumab, anti-TNF + tofacitinib) has emerging case-series evidence for severe refractory IBD. Rationale: different mechanisms may overcome mechanistic failure. Risks: increased infection (serious infection rates ~10%), financial toxicity, insurance denial. VEGA (UC) combined guselkumab + golimumab with favorable signal. Saudi IRB/MOH clearance required for non-label combinations. Reserve for: severe endoscopic disease, objective biochemical markers, failed ≥2-3 biologics, MDT consensus, informed consent.
Combination therapy is not standard of care — it requires local IRB approval, explicit informed consent about increased infection risk, and MDT consensus.
- Combination biologic for refractory IBD: emerging evidence
- VEGA positive signal in UC
- Serious infection rate ~10% with combination
- Requires Saudi IRB/MOH clearance
- Reserve for ≥2-3 biologic failures with MDT consensus
3Investigational and salvage therapies (30 min)
Fecal microbiota transplant (FMT): established in C. difficile, investigational in UC (mixed RCT data, Paramsothy meta-analysis positive; limited Saudi experience). Autologous hematopoietic stem-cell transplant (ASTIC trial for CD) — reserve for highly selected centers. CAR-T therapy for monogenic IBD research. Extracorporeal photopheresis: case series only. Total parenteral nutrition with bowel rest: temporary bridge. Clinical trial enrollment: SGA research committee can help identify open Saudi/regional trials.
Do not offer FMT for IBD outside a clinical trial in Saudi Arabia — regulatory pathway is still evolving and evidence is mixed.
- FMT investigational for UC; standard for recurrent C. difficile
- Autologous HSCT (ASTIC) for highly selected CD
- CAR-T for monogenic IBD in research
- TPN as temporary bridge
- Clinical trial enrollment through SGA research committee
4Surgery and palliation: when enough is enough (30 min)
After 2-3 biologic failures plus small-molecule failure in UC: colectomy with IPAA or end ileostomy is curative and quality-of-life improving. In CD: segmental resection if localized, multiple resections if extensive; counsel about short bowel risk. Discuss surgery early — do not wait until emergent. Palliation: pain management (avoid opioids long-term), nutrition optimization, psychological support, ostomy nurse involvement pre-op. Quality-of-life focus; symptom control over complete remission. Family support and spiritual care (particularly important in Saudi context).
In UC after multiple biologic failures, colectomy is CURATIVE — present it as a positive option to the patient rather than a failure of medical therapy.
- UC after 2-3 biologic+small molecule failure → colectomy is curative
- CD: segmental resection if localized; short-bowel risk with extensive
- Discuss surgery early, not as last resort
- Palliation: pain, nutrition, psychological, ostomy nurse
- Spiritual/family support is essential in Saudi context
- Always question the IBD diagnosis before declaring refractory — TB, Behçet, monogenic disease in Saudi Arabia
- Combination biologic therapy is emerging but requires IRB, MDT, and informed consent
- FMT is investigational in UC outside clinical trials in Saudi Arabia
- Surgery is curative in refractory UC — present as positive option, not failure
- Palliation emphasizes pain control, nutrition, psychology, and culturally-appropriate spiritual support
Assessment
Treatment algorithm design project + Safety monitoring checklist creation + MCQ
Clinical Pearls
Tofacitinib has the fastest onset of action — clinical response in days
Upadacitinib (selective JAK1) has better selectivity and possibly lower VTE risk than tofacitinib
S1P modulators require first-dose cardiac monitoring — lymphocyte sequestration is key mechanism
Herpes zoster risk is 2-3x higher with JAK inhibitors — consider Shingrix vaccination
Practice Points
Before tofacitinib/upadacitinib: assess VTE risk factors — avoid in high-risk patients
Before S1P modulators: obtain ECG, ophthalmology exam, check varicella immunity
JAK inhibitors are ORAL — major adherence advantage over IV/SC biologics
Key References
Sandborn WJ, et al. Tofacitinib for UC (OCTAVE). N Engl J Med. 2017;376:1723-1736
Danese S, et al. Upadacitinib for UC (U-ACHIEVE). Lancet. 2022;399:2113-2128
Sandborn WJ, et al. Ozanimod for UC (True North). N Engl J Med. 2021;385:1280-1291
Reading List
JAK inhibitors in IBD — mechanisms, efficacy, and safety
Olivera PA, et al. — Nat Rev Gastroenterol (2020)
S1P receptor modulators in IBD
Peyrin-Biroulet L, et al. — Lancet Gastroenterol (2021)
AGA Update on JAK Inhibitors in IBD
Lichtenstein GR, et al. — Gastroenterology (2023)
Combination advanced therapies in IBD — emerging evidence
Ahmed W, et al. — Clin Gastroenterol Hepatol (2024)