There is speculation that the use of therapeutic drug monitoring (TDM) may obviate the advantages of combination therapy. However, there is plenty of data supporting combination therapy including a recent retrospective population-based study (LE Targownik et al. Clin Gastroenterol Hepatol 2019; 17: 1788-98).

This ‘real-world’ study (2001-2016) utilized the Manitoba IBD database and included 852 persons with Crohn’s disease (CD) and 303 with ulcerative colitis (UC).

Key findings: 

• In persons with CD, combination therapy (immunomodulator with a TNF antagonist) was associated with lower treatment ineffectiveness with an adjusted hazard ratio (aHR) for ineffectiveness at 0.62.  The ineffectiveness in UC persons was lower at 0.82 but did not reach statistical significance.
• When looking at specific time frames, among patients with CD, at 1 year, combination therapy the rate of ineffectiveness-free treatment was 74.2% for combination therapy compared to 68.6% for monotherapy; at 2 years, the rates were 64.0% and 54.5% respectively.
• Combination therapy in CD was associated with increased time to first IBD-related hospitalization with aHR of 0.53 and with lower rates of switching anti-TNF agents (aHR 0.63).  Lower rate of surgery (aHR 0.76) did not reach statistical significance.
• The choice of immunomodulator (6-MP/AZA vs MTX) and the choice of anti-TNF agent (IFX or ADA) did not significantly influence the overall benefit of combination therapy.  Though, AZA was the main concomitant treatment (92%).
• 90% of the patients in the study who received combination therapy had received immunomodulator therapy prior to combination therapy.  This is in contrast to the SONIC study in which patients were naive to both agents.
• 57% of IFX users and 43% of ADA users received concomitant therapy.

My take: Combination therapy has been associated with higher response rates to IBD therapy.  This advantage has to be weighed against potential adverse effects.

Related blog posts:

• Combination Therapy Study Points to Central Role of Adequate TNF Levels
• Can Therapeutic Drug Monitoring with Monotherapy Achieve Similar Results as Combination Therapy in IBD?
• Digging into the COMMIT study
• Don’t be Fooled About Withdrawing Immunomodulator Cotherapy -Look Past the Headline
• Methotrexate –First Choice Immunomodulator? | gutsandgrowth
• Should All Pediatric Patients with Crohn’s Disease Continue Combination Therapy? | gutsandgrowth
• ‘Don’t Believe Our Study’ | gutsandgrowth
• Changes in the Use of IBD Biologic Therapy | gutsandgrowth
• Toronto Consensus: Practice Guidelines for Nonhospitalized Ulcerative Colitis | gutsandgrowth

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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