A recent intriguing retrospective study (MJ Casanova et al. Inflamm Bowel Dis 2020; 26: 606-16, editorial 617-18) examines a large cohort (n=1122) who received either a 2nd or 3rd anti-TNF agent.  This relied on the ENEIDA registry which is a prospectively maintained registry from Spain with 11,866 patients. In this study, clinical remission was gauged with a Harvey Bradshaw Index score of ≤4 in Crohn’s disease (CD) or a partial Mayo score of ≤2 in ulcerative colitis (UC).

Key findings:

• 45% of patients achieved remission with the second anti-TNF at 12 weeks (short-term); loss of response was 19% per patient-year subsequently. Patients with intolerance to the first drug had higher remission rates compared to those who switched due to secondary failure (52% vs 42%) or primary failure (52% vs 39%).
• Among the 45% who responded to a second anti-TNF agent, 77% maintained remission at 1 year following switch.
• There was similar initial response to a second anti-TNF among patients with CD and UC: 46% vs 41%, though patients with UC were more likely to lose efficacy.
• Combination therapy was associated with a higher likelihood of failure, HR 2.4 (possibly as an indicator of more aggressive disease)
• Among the 71 patients who progressed to a 3rd anti-TNF agent, 55% achieved remission at 12 weeks. 

Discussion:

• The authors in their discussion not that “primary failure is considered a class effect phenomenon…However, our results indicate that remission may still be achieved with a second anti-TNF in approximately 50% of patients.”
• The editorial notes that the results need to be interpreted with caution.  Therapeutic drug monitoring (TDM) which is not incorporated in this study is crucial in optimizing response and switching.  “Importantly, nearly two-thirds of patients with therapeutic drug levels in the study form the Mayo Clinic had no active inflammation.  Thus, a change in therapy would be inappropriate in this population.”

My take: This study indicates that a 2nd anti-TNF agent can be effective in those who do not respond to a 1st.  At the same time, careful assessment including TDM is needed when changing agents, especially in view of the limited number of effective therapies.

Related blog posts:

• Here’s the Proof That Proactive Drug Monitoring Works in Children With Crohn’s Disease
• CCFA 2019 Update: Proactive Therapeutic Drug Monitoring
• Appropriate Proactive Therapeutic Drug Monitoring
• Briefly noted: Induction Infliximab Levels
• “Silent” Crohn’s Disease | gutsandgrowth

• Do Anti-TNF Agents Reduce Surgeries and Hospitalizations?
• Top Anti-TNF for Ulcerative Colitis
• Gold Medal Winner: Infliximab (in the anti-TNF category) this post initially was during 2016 Olympics
• Comparing Biologics for Ulcerative Colitis | gutsandgrowth
• Head-to-Head: Nutritional Therapy versus Biological … – gutsandgrowth
• Adalimumab for children with Crohn’s disease | gutsandgrowth
• Should All Pediatric Patients with Crohn’s Disease … – gutsandgrowth
• What is Your Infliximab Adherence Rate? | gutsandgrowth
• Changes in the Use of IBD Biologic Therapy

From Atlanta Botanical Garden