What is the data on Adalimumab (adalimumab) in Crohn's disease (CD) and ulcerative colitis (UC)?

Efficacy and Safety of Adalimumab in Crohn's Disease and Ulcerative Colitis

Adalimumab demonstrates significant efficacy for induction and maintenance of remission in Crohn's disease (CD), but shows lower efficacy in ulcerative colitis (UC) compared to other biologics like infliximab and vedolizumab. 1

Efficacy in Crohn's Disease

• Adalimumab is effective for induction of clinical remission in moderate-to-severe CD with a relative risk of 3.58 (95% CI: 2.42–5.29) compared to placebo within 4 weeks of therapy initiation 1
• Clinical response rates with adalimumab reach 81.8% at 8 weeks and 84.4% at 12 weeks in patients with active luminal CD 2
• For maintenance therapy, adalimumab demonstrates efficacy over placebo with a relative risk of 2.70 (95% CI: 1.75–4.19) for maintaining clinical remission at 52-56 weeks 1
• Endoscopic outcomes show significant improvement with adalimumab compared to placebo:
  • Endoscopic remission: RR 9.14 (95% CI: 2.21–37.80)
  • Endoscopic response: RR 14.22 (95% CI: 1.93–104.98)
  • Mucosal healing: RR 31.00 (95% CI: 1.90–506.95) 1
• In patients who previously lost response to infliximab, adalimumab achieves response rates of 86.7% and remission rates of 53.3% at 12 weeks 2
• Long-term data from the ADHERE study shows sustained clinical response and remission rates of 39.0% and 26.5%, respectively, at 96 weeks in patients who previously failed infliximab 3

Efficacy in Ulcerative Colitis

• In UC, adalimumab shows more modest efficacy compared to CD:
  • ULTRA1 trial: 19% remission rate at week 8 (vs. 9% placebo)
  • ULTRA2 trial: 21% remission rate at week 8 (vs. 11% placebo) in anti-TNF naïve patients 1
• Maintenance efficacy in UC at week 52 shows:
  • Clinical remission: 22% (vs. 12% placebo) in anti-TNF naïve patients
  • Corticosteroid-free remission: 14% (vs. 6% placebo) 1
• In the ULTRA3 extension study, 25% of patients maintained clinical remission at 4 years 1
• The AGA guidelines suggest using infliximab or vedolizumab rather than adalimumab for induction of remission in moderate-severe UC (conditional recommendation, moderate quality evidence) 1
• In the head-to-head VARSITY trial, vedolizumab demonstrated superior clinical remission rates compared to adalimumab (34.2% vs. 24.3%) in biologic-naïve UC patients 1
• Network meta-analyses suggest infliximab is superior to adalimumab for induction of remission in UC (OR: 2.10; 95% CI: 1.16-3.79) 1

Combination Therapy vs. Monotherapy

• Post-hoc analyses of clinical trials show no significant efficacy benefits with adalimumab/immunomodulator combination therapy compared to adalimumab monotherapy in both CD and UC patients who had inadequate response to conventional therapy 4
• Adalimumab concentrations at weeks 4-8 are numerically but not significantly higher with combination therapy versus monotherapy 4
• The combination of anti-TNF therapy with thiopurines is associated with increased risk of serious infections and malignancies, though absolute rates remain very low 1

Safety Profile

• The safety profile of adalimumab is generally favorable:
  • No significant difference in adverse events between adalimumab and placebo during induction (RR: 0.91; 95% CI: 0.75-1.11) 1
  • Long-term safety data from 16 clinical trials (CD: 4145 patient-years; UC: 3397 patient-years) show:
    • Serious adverse events: 36.1 events/100 patient-years in CD and 18.9 events/100 patient-years in UC
    • Malignancies: 1.2 events/100 patient-years in CD and 1.0 events/100 patient-years in UC
    • Opportunistic infections: 0.3 events/100 patient-years in CD and 0.2 events/100 patient-years in UC 5
  • Standardized incidence ratios for malignancies were similar to the general population (CD: 1.45 [95% CI: 0.90-2.22]; UC: 1.36 [95% CI: 0.84-2.07]) 5
  • Demyelinating disorders are uncommon (CD: 0.1 events/100 patient-years; UC: <0.1 events/100 patient-years) 5

Clinical Considerations and Dosing

• Standard induction dosing for adalimumab in CD and UC is 160 mg at week 0,80 mg at week 2, followed by 40 mg every other week 1
• Patients with limited response at 8 weeks may benefit from dose escalation to weekly administration 2
• Adalimumab is not recommended for acute severe UC, as there are insufficient data supporting its use in this setting 1
• For patients who value convenience of self-administered subcutaneous injections over slightly higher efficacy, adalimumab may be a reasonable alternative to infliximab or vedolizumab, particularly in those with less severe disease 1

Monitoring and Optimization

• Response to adalimumab therapy should be evaluated at 8-12 weeks to determine the need for treatment modification 1
• Quality of life improvements are observed within 4 weeks of therapy initiation based on IBDQ scores 1
• Therapeutic drug monitoring may be useful to optimize dosing, though specific target levels are still being established 1