Role of Adalimumab in Treating Moderate to Severe Ulcerative Colitis
Adalimumab is suggested as a second-line option for moderate to severe ulcerative colitis, with lower efficacy compared to other biologics like infliximab and vedolizumab, but may be considered for patients who prioritize the convenience of self-administered subcutaneous injections. 1
Efficacy and Positioning in Treatment Algorithm
The American Gastroenterological Association (AGA) classifies adalimumab as a "LOWER efficacy medication" compared to "HIGHER efficacy" options (infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab) and "INTERMEDIATE efficacy" options (golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab) 1
In biologic-naïve patients, infliximab demonstrated superiority over adalimumab (OR, 2.10; 95% CI, 1.16–3.79) in network meta-analyses 1
In head-to-head trials (VARSITY), vedolizumab showed significantly higher clinical remission rates compared to adalimumab (34.2% vs. 24.3%; RR, 1.41; 95% CI, 1.10–1.81) in biologic-naïve patients 1
Despite lower efficacy, adalimumab remains a viable option for patients who value the convenience of self-administered subcutaneous injections, particularly those with less severe disease 1
Dosing and Administration
Standard induction regimen: 160 mg at week 0,80 mg at week 2, followed by 40 mg every other week starting at week 4 2, 3
Higher induction regimen (160 mg at weeks 0,1,2, and 3) did not show statistically significant improvement in clinical remission at week 8 compared to standard induction (13.3% vs 10.9%, P = .265) 4
Mean steady-state trough concentrations were approximately 8 mcg/mL at Week 52 with 40 mg every other week dosing and approximately 15 mcg/mL with 40 mg weekly dosing 2
Weekly dosing (40 mg every week) showed a trend toward higher clinical remission rates at week 52 compared to every-other-week dosing (41.1% vs 30.1%, nominal P = .045) in the SERENE UC trial 4
Clinical Outcomes
Adalimumab is effective for both induction and maintenance of remission in patients with moderate to severe UC who have not responded adequately to conventional therapy with steroids or immunosuppressants 3
Overall rates of clinical remission at week 8 were 16.5% with adalimumab versus 9.3% with placebo (P = .019); corresponding values for week 52 were 17.3% versus 8.5% (P = .004) 3
Adalimumab is associated with significant reductions in risk of all-cause (40%), UC-related (50%), and UC- or drug-related (47%) hospitalizations within the first 8 weeks of therapy compared to placebo (P < .05 for all comparisons) 5
In patients who previously responded to infliximab and then lost response or became intolerant, adalimumab may help avoid colectomy in approximately half of patients 6
Special Populations and Considerations
In anti-TNF-naïve patients, remission rates at week 8 were 21.3% on adalimumab versus 11% on placebo (P = .017); corresponding values for week 52 were 22% versus 12.4% (P = .029) 3
In patients previously exposed to anti-TNF agents, particularly those with primary non-response to infliximab, the AGA suggests using ustekinumab or tofacitinib rather than adalimumab or vedolizumab 1
Combining TNF antagonists (including adalimumab) with immunomodulators is suggested over TNF antagonist monotherapy or immunomodulator monotherapy 1
In patients with moderate-to-severe UC who are in corticosteroid-free clinical remission for at least 6 months on combination therapy of TNF antagonists and an immunomodulator, the AGA suggests against withdrawal of TNF antagonists 1
Safety Profile
Adalimumab is generally well-tolerated with a safety profile similar to that observed in other approved indications 7
Serious adverse events occurred in 12% of patients given adalimumab or placebo in clinical trials 3
Serious infections developed in 1.6% of patients given adalimumab and 1.9% given placebo 3
Anti-adalimumab antibodies may develop and are associated with reduced serum adalimumab concentrations, potentially affecting clinical efficacy 2
Common Pitfalls and Caveats
Adalimumab may be less effective than other biologics but should not be overlooked for patients who prioritize the convenience of self-administration 1
Drug concentrations were not optimized in clinical trials; efficacy of adalimumab may be comparable to other TNF antagonists when adequate drug concentrations are achieved 1
Early response to adalimumab is predictive of long-term efficacy, suggesting that treatment decisions should be reassessed early in the course of therapy 7
Anti-drug antibodies can reduce adalimumab concentrations and efficacy, highlighting the potential benefit of combination therapy with immunomodulators 2