Reply to Blom: Drugs Do Not Work in Patients Who Cannot Tolerate Them

We are pleased to know that Dr. Dirk Blom, a key contributor to the pivotal trial of lomitapide,[1] took the time to read our paper[2] detailing the experience with the drug at King Abdulaziz Medical City.[3]We agree with the necessity for additional therapies beyond triple therapy (statin, ezetimibe, and a PCSK9 inhibitor) and that a fourth line is typically needed to further lower low-density lipoprotein cholesterol (LDL-C) levels in patients with homozygous familial hypercholesterolemia (HoFH). The inconvenience of lipid apheresis and its toll on the quality of life of patients, despite being the most effective in reducing the LDL-C, is often impractical and refused by patients. Oral administration of lomitapide is a convenience but might be slightly inflated over other factors, such as its tolerability and high cost, which would offset travel expenses for remote patients when compared with a once-monthly infusion.We were similarly disappointed by the real-world effectiveness of lomitapide, which did not align with the results reported in its registration study.[1] In response to the inquiry about the doses reached, the doses reached by each patient 1 month before their LDL-C levels were measured are shown in Figure 1. Of the eight patients, only two reached the 40-mg dose, and six were maintained at 20 mg; all eight patients completed an initial titration phase. Upon closer examination of the trends for patients 1 and 5 who reached a 40-mg dose, the disappointment grows. We believe that noncompliance contributed to these trends, which were assessed accurately and comprehensively to make an informed formulary decision.It is also noteworthy that our patient population is often excluded from trials or, when included, is racially miscategorized.[4] Therefore, pharmacogenetic factors influencing drug response are also a plausible reason. The recent initiatives outlined in Saudi Arabia's Vision 2030, aimed at transforming the health sector and promoting local research while fostering participation in global clinical trials, could address such issues.[5–8]Therefore, we agree with the statement quoted in the response letter, "Drugs don't work in patients who don't take them," but would add that "Drugs don't work in patients who cannot tolerate them."