X Roblin et al. Inflamm Bowel Dis 2022; 28: 720-727. Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels
Many times, treatment decisions are like on “Let’s Make a Deal.” That is, should I stick with what I’ve got or should I try for something better & sometimes wind up with a goat. In this referenced article, patients were under maintenance therapy with adalimumab (ADA) monotherapy (40 mg every 14 days) and had experienced a secondary loss of response (LOR) despite trough levels > 4.9 μg/mL. In this nonrandomized prospective study, patients were either swapped to vedolizumab (VDZ) or optimized on adalimumab (ADA) treatment.
- At 24 months, 11 out of 70 patients (16%) in the swap group discontinued treatment compared with 36 out of 61 (59%) patients in the optimization group (P < 0.001)
- In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.5)
- In patients selected for optimization, 56% (34/61) remained on ADA at 1 year and 41% (25/61) at 2 years
In their discussion, the authors state “current guidelines recommend switching to another class of biologics in case of LOR to ADA with therapeutic drug levels.” However, the authors note that their therapeutic level cut-off of >4.9 mcg/mL is lower than the latest recommendations. In addition, in their conclusion, they note that due to limited biologic options, “ADA optimization strategy might be considered” in a subgroup.
My take: Despite better results in the patients that swapped to VDZ in this study, I think it is important to assure adequate drug levels before choosing a new drug class. For ADA, expert recommendations have suggested a level of 8-12 as therapeutic and to avoid discontinuation if ADA level is less than 10. In this study, more than 40% remained on ADA two years after LOR in those with dosing optimization.
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Maximizing therapeutic drug level definitely seems important, however, the FDA is not seeing it that way or is behind the times. Insurance seems to be standing firm on drug levels of under 10 and generally 5-8 as an FDA guideline and won’t allow increased dosing regimens. Not sure if there is any push with drug levels and the FDA for broader range in the pediatric population? Seems like a great place for Humira and Remicade to get back some market share over biosimilars?
I also get pushback on giving therapeutic doses from insurance companies. Though, I’ve had some success lately with insurers by citing expert guidelines on dosing: AS Cheifetz et al. Am J Gastroenterol 2021;116: 2014-2025 (Blog post: Expert Consensus: New Recommendations for Therapeutic Drug Monitoring)