What are the recent updates in the management of ulcerative colitis?

Recent Updates in Management of Ulcerative Colitis

The most significant recent update is the expansion of first-line advanced therapy options for moderate-to-severe ulcerative colitis, with infliximab, vedolizumab, ustekinumab, tofacitinib, and newer agents like upadacitinib, risankizumab, guselkumab, and ozanimod now recommended over traditional step-up approaches in biologic-naïve patients. 1, 2

Advanced Therapy Selection for Moderate-to-Severe Disease

First-Line Biologic-Naïve Patients

For biologic-naïve patients with moderate-to-severe UC, infliximab, risankizumab, guselkumab, or ozanimod demonstrate superior efficacy for inducing clinical remission compared to adalimumab and should be prioritized. 2

• The AGA strongly recommends using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment (strong recommendation, moderate quality evidence). 1
• Infliximab or vedolizumab are suggested over adalimumab for induction of remission in biologic-naïve patients, though patients valuing convenience of subcutaneous self-injection may reasonably choose adalimumab. 1
• Newer agents including upadacitinib, risankizumab, and ozanimod are now recommended as first-line options outside the United States. 2

Post-Infliximab Failure Strategy

• In patients with prior infliximab exposure, particularly primary non-responders, ustekinumab or tofacitinib are suggested over vedolizumab or adalimumab for induction of remission (conditional recommendation, low quality evidence). 1

Combination Therapy vs. Monotherapy

Combining TNF antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate is superior to biologic monotherapy for inducing remission. 1, 2

• The AGA suggests combination therapy rather than biologic monotherapy, though patients with less severe disease who place higher value on safety may reasonably choose monotherapy (conditional recommendation, low quality evidence). 1
• This represents a shift toward optimizing efficacy through combination approaches, particularly for infliximab. 1

Early Biologic Use vs. Step-Up Approach

Early use of biologic agents with or without immunomodulator therapy is now recommended over gradual step-up after failure of 5-aminosalicylates in patients with moderate-severe disease at high risk of colectomy. 1

• This paradigm shift moves away from traditional step-up therapy, recognizing that delayed advanced therapy in high-risk patients leads to worse outcomes. 1
• Patients in remission on biologics and/or immunomodulators after prior 5-ASA failure may discontinue 5-aminosalicylates. 1

JAK Inhibitor Positioning

Tofacitinib should only be used after failure of or intolerance to TNF antagonists, not as first-line therapy in biologic-naïve patients. 1

• Updated FDA recommendations (July 2019) restrict tofacitinib use to patients who have failed TNF antagonists due to safety concerns. 1
• The AGA recommends tofacitinib be used in biologic-naïve patients only within clinical or registry studies (knowledge gap). 1
• Newer JAK inhibitors (upadacitinib, filgotinib) are similarly recommended only after prior TNF antagonist failure or intolerance. 2

Acute Severe Ulcerative Colitis Management

Initial Treatment

• Intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 100 mg four times daily) remains the mainstay of initial therapy for hospitalized ASUC patients. 1, 2
• Routine adjunctive antibiotics are not recommended in patients without documented infections. 1
• Thromboprophylaxis with low-molecular-weight heparin is essential, as rectal bleeding is not a contraindication. 1, 2

Rescue Therapy Timing

Patients refractory to 3-5 days of intravenous corticosteroids should receive rescue therapy with either infliximab or cyclosporine rather than prolonging ineffective steroid therapy. 1, 2

• Early assessment (day 3-5) for steroid response is critical—predictors of failure include >8 stools/day or 3-8 stools/day with CRP >45 mg/L on day 3. 2
• No recommendation can be made regarding intensive vs. standard infliximab dosing in ASUC. 1
• Prolonged corticosteroid courses beyond 7-10 days offer no additional benefit and increase toxicity. 2

Biosimilars and Treatment Equivalence

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs and represent a cost-effective option. 2

Immunomodulator Monotherapy

Thiopurine monotherapy is not recommended for induction of remission in active moderate-severe UC but may be used for maintenance in patients already in remission. 1

• The AGA suggests against thiopurine monotherapy for induction (conditional recommendation, very low quality evidence). 1
• For maintenance of remission, thiopurine monotherapy is suggested over no treatment (conditional recommendation, low quality evidence). 1
• Methotrexate monotherapy is not recommended for either induction or maintenance of remission (conditional recommendation, low quality evidence). 1

Treatment Monitoring and Targets

• Response should be determined by combining clinical parameters, endoscopy, and laboratory markers such as CRP and fecal calprotectin. 3
• Mucosal healing should be assessed endoscopically or by fecal calprotectin approximately 3-6 months after treatment initiation in patients who respond clinically. 3
• Mucosal healing is associated with reduced colectomy risk and lower inflammation at 5 years. 3

Common Pitfalls

• Do not delay rescue therapy in ASUC—patients remaining on ineffective corticosteroids beyond day 5 suffer high morbidity and delayed surgery. 1
• Do not switch between different oral 5-ASA formulations if initial therapy fails—this approach is ineffective. 2
• Do not use anti-diarrheal medications in severe UC—they may precipitate toxic megacolon. 2
• Do not withdraw TNF antagonists in patients on combination therapy who achieve corticosteroid-free remission for ≥6 months—maintain the TNF antagonist. 2

Emerging Treatment Targets

• Treatment targets are evolving beyond clinical remission to include endoscopic remission, with ongoing investigation into whether histologic remission provides incremental benefit. 1
• Biomarkers predictive of response to individual therapies remain a critical knowledge gap requiring future research. 1