Is Skyrizi (Risankizumab-rzaa) infusion therapy medically necessary for a patient with a history of ulcerative pancolitis and mild current symptoms?

Medical Necessity Assessment for Skyrizi (Risankizumab) in Ulcerative Pancolitis

Skyrizi infusion therapy is medically necessary and represents standard of care for this patient with ulcerative pancolitis who has failed adalimumab therapy, demonstrated objective evidence of ongoing inflammation (elevated fecal calprotectin 331 mg/g), and has subtherapeutic adalimumab levels indicating treatment failure. 1, 2

Evidence of Active Disease Requiring Treatment Escalation

The insurance denial citing "no active reports of moderate to severe ulcerative colitis" misinterprets the clinical picture:

• Fecal calprotectin of 331 mg/g is significantly elevated (>150 mg/g threshold), indicating active intestinal inflammation that warrants treatment adjustment per AGA guidelines 3
• Subtherapeutic adalimumab levels (3.1 mcg/mL) without antibodies document primary non-response or loss of response, necessitating switch to an alternative mechanism of action 1
• Recent colonoscopy showing erythema compatible with mild ulcerative colitis provides endoscopic confirmation of ongoing disease activity 3
• The patient's history includes documented moderate-to-severe proctitis on prior colonoscopy, establishing disease severity 3

The combination of elevated biomarkers, endoscopic inflammation, and biologic failure meets criteria for advanced therapy escalation even in the absence of severe symptoms. 3

Guideline Support for Risankizumab

Strong Recommendation from AGA

• The American Gastroenterological Association strongly recommends risankizumab for moderate-to-severe ulcerative colitis over no treatment (strong recommendation, moderate to high certainty of evidence) 1
• This recommendation applies to patients who have failed prior biologic therapy, which describes this patient's clinical scenario 1

FDA-Approved Indication and Dosing

• The proposed regimen (1200 mg IV at weeks 0,4, and 8) matches the FDA-approved induction dosing for moderately to severely active ulcerative colitis 2
• Phase III trials demonstrated 20.3% clinical remission at week 12 with risankizumab versus 6.2% with placebo (p<0.001) 2, 4
• Among patients with prior biologic failure (like this patient), risankizumab achieved 36.5% endoscopic improvement versus 12.1% with placebo 1

Treatment Escalation is Standard of Care

British Society of Gastroenterology guidelines explicitly state:

• Patients requiring two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent or refractory, require treatment escalation with thiopurine, anti-TNF therapy, vedolizumab, or other advanced biologics 3
• This patient has failed mesalamine and adalimumab, developed a drug-related rash, and has objective evidence of ongoing inflammation—meeting escalation criteria 3

Biomarker-Guided Treatment Decisions

The AGA 2023 biomarker guidelines support this treatment decision:

• In patients with elevated fecal calprotectin (>150 mg/g), treatment adjustment is appropriate without requiring repeat endoscopy solely to establish disease presence 3
• The guideline specifically notes that when making significant treatment decisions such as starting or switching immunosuppressive therapies, biomarkers combined with prior endoscopic findings are sufficient 3
• This patient has both elevated calprotectin AND recent endoscopic confirmation of inflammation 3

Comparative Efficacy Data

Recent network meta-analysis demonstrates:

• Risankizumab ranked second (91.4%) for inducing clinical remission and second (82.3%) for endoscopic improvement among all biologics and small molecules 5
• Risankizumab ranked first (89.4%) for inducing histological remission, followed by guselkumab 5
• These data support risankizumab as an appropriate choice after anti-TNF failure 5

Safety Requirements Met

All prerequisite safety screening has been completed:

• Negative tuberculosis testing documented (TB Gold plus negative) as required before initiating IL-23 inhibitor therapy 6, 2
• Hepatitis B and C screening completed (all negative) 2
• No contraindications such as active sepsis or serious infection present 6

Clinical Pitfalls to Avoid

Common insurance denial error: Requiring "moderate to severe symptoms" while ignoring objective biomarkers of inflammation. The AGA explicitly recommends combining biomarkers with symptoms rather than relying on symptoms alone, specifically to avoid undertreatment of patients with subclinical inflammation 3.

The patient is currently asymptomatic because he is only 2 months off adalimumab—the elevated calprotectin predicts imminent clinical relapse if left untreated. Waiting for symptom development before initiating therapy contradicts treat-to-target principles and risks disease progression 3.

Answers to Specific Questions

1. Is the treatment plan medically necessary?

Yes, absolutely. The patient has documented ulcerative pancolitis with objective evidence of active inflammation (fecal calprotectin 331 mg/g, endoscopic erythema), failed adalimumab therapy with subtherapeutic drug levels, and meets criteria for advanced biologic therapy per AGA guidelines 3, 1. Delaying treatment risks disease progression, hospitalization, and potential colectomy 3.

2. Is the treatment plan standard of care or experimental?

This is standard of care, not experimental. Risankizumab received FDA approval for moderately to severely active ulcerative colitis in 2022 based on two phase III randomized controlled trials 2, 4. The American Gastroenterological Association issued a strong recommendation for risankizumab in moderate-to-severe UC in 2023 1. The British Society of Gastroenterology guidelines recognize risankizumab as an effective treatment option for UC patients who have failed conventional and anti-TNF therapies 1. The proposed dosing regimen (1200 mg IV at weeks 0,4, and 8) is the FDA-approved induction regimen 2, 7.