Can long-term use of prednisone (corticosteroid) at high doses in patients with ulcerative colitis lead to mortality and if so, what percentage of patients are at risk?

Long-Term High-Dose Prednisone and Mortality in Ulcerative Colitis

Yes, long-term prednisone use at high doses is associated with increased mortality in patients with ulcerative colitis, with overall mortality in acute severe UC at 1%, though prolonged steroid use (>3000 mg prednisolone equivalent per year) carries significantly greater mortality risk compared to patients starting anti-TNF therapy. 1

Mortality Data and Risk Stratification

Overall Mortality Rates

• Acute severe ulcerative colitis (ASUC) carries an overall mortality of 1% (22/1991 patients; 95% CI 0.7% to 1.6%) across multiple studies from 1974-2006, with this rate remaining unchanged over time. 1
• Mortality is significantly higher in elderly patients compared to younger patients with ASUC. 1
• In the TREAT registry examining Crohn's disease patients, prednisone therapy was associated with increased mortality (hazard ratio 2.14; 95% CI 1.55-2.95; P < 0.001). 1

High-Dose and Prolonged Use Risks

• Prolonged steroid use (defined as >3000 mg prednisolone equivalent in 1 year) carries greater mortality in IBD patients, with this effect being statistically significant for Crohn's disease and non-significant but trending toward increased mortality in UC. 1
• Prednisolone use was identified as an independent risk factor for mortality in IBD patients. 1
• Prolonged use beyond 3 months is associated with numerous life-threatening complications including increased infection risk, osteoporosis, suppression of the hypothalamic-pituitary-adrenal axis, diabetes, weight gain, and cardiovascular disease. 1

Clinical Context and Treatment Duration Limits

Maximum Safe Duration

• Intravenous corticosteroid courses beyond 7-10 days carry no additional benefit and increase toxicity. 1, 2
• Oral corticosteroid courses should not exceed 6-8 weeks, with tapering initiated as soon as clinically appropriate. 1, 2
• Higher doses above 60 mg/day methylprednisolone (or 40-60 mg/day prednisone) offer no additional advantage and are associated with increased adverse events. 1

Infection-Related Mortality

• Prednisone therapy is associated with increased risk of serious infections (hazard ratio 1.57; 95% CI 1.17-2.10; P = 0.002). 1
• Case reports document fatal opportunistic infections including MRSA and Pseudomonas aeruginosa in UC patients on high-dose steroids combined with immunosuppressants. 3, 4

Steroid Dependency and Long-Term Outcomes

Prevalence of Problematic Steroid Use

• 14.9% of IBD patients have steroid dependency or excess in the UK, more commonly in UC than Crohn's disease. 1
• Steroid dependency is defined as inability to wean below 10 mg prednisolone within 3 months or disease flare within 3 months of stopping. 1
• Approximately 50% of UC patients responding to a first corticosteroid course will require immunosuppressors due to steroid-dependence. 5

Colectomy Risk

• Around one-fifth of patients hospitalized with ASUC require subtotal colectomy during the same admission. 1
• The risk of colectomy increases after subsequent episodes of ASUC. 1
• Over 5 years, only 50% of initial responders to rescue therapy avoid colectomy. 4

Critical Clinical Pitfalls to Avoid

Delayed Treatment Escalation

• Patients remaining on ineffective corticosteroid therapy suffer high morbidity associated with delayed surgery. 1
• In an audit, excessive steroid use was avoidable in nearly half of patients, particularly when patients attended dedicated IBD clinics with multidisciplinary teams. 1
• Patients not responding after 2 weeks of oral prednisolone 40 mg/day should be considered for treatment escalation to biologics or hospital admission. 1

Treatment Escalation Algorithm

For patients requiring corticosteroids beyond initial induction:

• After 3-5 days of IV steroids without response, consider salvage therapy (infliximab, vedolizumab, tofacitinib) or surgery. 1
• For steroid-dependent patients (two or more courses in past year), escalate to thiopurines, anti-TNF therapy, vedolizumab, or tofacitinib rather than continuing steroids. 1
• Never use corticosteroids for maintenance therapy as they are ineffective for preventing relapse and carry unacceptable long-term risks. 1

Monitoring Requirements During Necessary Steroid Use

• Baseline and annual bone mineral density testing for patients on long-term therapy. 2
• Regular blood glucose monitoring due to diabetes risk. 2
• Frequent blood pressure evaluations as hypertension develops rapidly. 2
• Ophthalmologic exams for cataracts and glaucoma if therapy continues beyond 6 weeks. 2

Bone Protection and Complication Prevention

• Approximately 35-40% of IBD patients suffer from osteopenia and 15% from osteoporosis, with prolonged or high-dose corticosteroids being a major risk factor. 1
• Bisphosphonates are strongly recommended for preventing osteoporosis in high-risk patients. 2
• Calcium (500-1000 mg daily) and vitamin D (800 IU daily) supplementation should be provided to all patients on corticosteroids. 1