Impact of body mass index on the severity of bexarotene‐associated hypertriglyceridemia: A post hoc analysis of an open‐labeled clinical study of combined bexarotene and phototherapy in Japanese patients with cutaneous T‐cell lymphoma

Abstract

Bexarotene is an effective oral drug for the treatment of cutaneous T‐cell lymphoma, but careful management is required due to its various side effects. In particular, hypertriglyceridemia often requires a reduction or even suspension of bexarotene therapy. The risk factors of bexarotene‐associated severe hypertriglyceridemia are not clear. Here, we conducted a post hoc analysis of the data from our previous clinical trial, which confirmed the efficacy and safety of combined bexarotene and phototherapy, to evaluate the effect of body mass index on bexarotene‐associated hypertriglyceridemia. Twenty‐five subjects were divided into two subgroups: normal and underweight (body mass index [BMI] <25 kg/m2 group) and overweight and obese (BMI ≥25 kg/m2 group) patients. The overall incidence of hypertriglyceridemia was 81.3% (13/16) in the BMI <25 kg/m2 group and 88.9% (8/9) in the BMI ≥25 kg/m2 group. The incidence of grade ≥3 hypertriglyceridemia (≥500 mg/dL) was 7.7% (1/13) in the BMI <25 kg/m2 group and 7/8 (87.5%) in the BMI ≥25 kg/m2 group (P < 0.001). Consequently, dose reduction in the BMI ≥25 kg/m2 group was larger than that in the BMI <25 kg/m2 group. The bexarotene‐induced change in the serum triglyceride concentration was significantly increased in cutaneous T‐cell lymphoma patients with a higher body mass index (ρ = 0.508, P = 0.009). The area under the curve was 0.886 (95% confidence interval 0.748–1.000, P = 0.002). With a body mass index cut‐off of 24.85 kg/m2, the sensitivity and specificity for identifying grade ≥3 hypertriglyceridemia were 0.875 and 0.882, respectively. The present findings suggest that BMI ≥25 kg/m2 is a risk factor for bexarotene‐associated severe hypertriglyceridemia, therefore overweight and obese patients treated with bexarotene should receive lipid‐lowering drugs prophylactically. Further studies for optimizing the initial bexarotene dose in such patients are required.

Effects of Body Mass Index on Hypertriglyceridemia Associated with Oral Bexarotene Therapy: A Post Hoc Analysis of an Open-Label Comparative Clinical Study of Combined Bexarotene and Phototherapy Versus Bexarotene Monotherapy for Japanese Patients with Cutaneous T-Cell Lymphoma

“…Using a BMI cutoff value of 23.80 kg/m 2 , the sensitivity and specificity were 0.538 and 0.500, respectively. These results differed from our previous findings that suggested that high BMI predicted severe hypertriglyceridemia for all patients and those who received combined bexarotene and phototherapy [13], thus implying that high BMI is a potential risk factor for hypertriglyceridemia and additional unidentified risk factors may exist.…”

“…The BMI cut-off value of 23 kg/m 2 , which was associated with severe bexarotene-associated hypertriglyceridemia in this study, is similar to the criteria for overweight in Asian countries [15][16][17]. As mentioned, our previous study suggested a potential relationship between BMI ≥25 kg/m 2 and severe bexarotene-associated hypertriglyceridemia [13]. These varying results suggested that the BMI cut-off value for severe bexarotene-associated hypertriglyceridemia in Asian countries, including Japan, may be between 23 and 25.…”

“…The present study analyzed the results of an open-label study of combined bexarotene and phototherapy and bexarotene monotherapy for Japanese patients with CTCL to verify the hypotheses proposed by that study [13]. Initially, our previous study established a relationship between high BMI and severe bexarotene-associated hypertriglyceridemia in patients who received combined bexarotene and phototherapy [13].…”

“…This trend was also observed after bexarotene monotherapy. In our previous study, patients with high BMI had a more substantial bexarotene dose reduction [13]. The initial and final body surface area-based doses of bexarotene and the reductions of these doses in the BMI <23 kg/m 2 and BMI ≥23 kg/m 2 groups were not statistically significant.…”

“…In our previous study, severe hypertriglyceridemia frequently occurred in patients with body mass index (BMI) ≥25 kg/m 2 ; additionally, bexarotene dose reduction was performed frequently for these patients. Surprisingly, despite dose reductions, few differences in efficacy at 24 weeks were observed in patients in the BMI <25 kg/m 2 and BMI ≥25 kg/m 2 groups [13]. Although that study generated hypotheses regarding bexarotene and BMI, it had several limitations, including a small sample size and single-arm study design involving combined bexarotene and phototherapy.…”