The effect of temperature on the stability of PCSK-9 monoclonal antibody: an experimental study.

BACKGROUND: PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2-8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries. METHODS: Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA. RESULTS: Average subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was - 5.8 ± 4.4% (P = 0.005) and - 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and - 9.7 ± 11.8% (P = 0.04) and - 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were - 5.2 ± 2.9% (P = 0.001) and - 2.6 ± 4.9% (P = 0.16) for alirocumab, and - 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab. CONCLUSION: Proper drug storage according to manufacturer's recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.

Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report.

BACKGROUND: Elevated plasma cholesterol and/or plasma triglyceride levels in nephrotic syndrome patients are the result of impaired lipoprotein clearance and a compensatory increase in hepatic lipoprotein synthesis. Plasma proprotein convertase subtilisin/kexin type 9 levels directly correlate to the amount of proteinuria in nephrotic syndrome patients. Proprotein convertase subtilisin/kexin type 9 monoclonal antibody has been used to treat dyslipidemia in some refractory nephrotic syndrome cases. As a therapeutic protein, proprotein convertase subtilisin/kexin type 9 monoclonal antibody simply deteriorates if stored in inappropriate temperatures or conditions. CASE PRESENTATION: In this article, we present the case of a 16-year-old Thai female with severe combined dyslipidemia secondary to refractory nephrotic syndrome. She received proprotein convertase subtilisin/kexin type 9 monoclonal antibody (alirocumab) treatment. However, the drugs were mistakenly frozen in a freezer for up to 17 hours before being stored at 4 °C. After using two frozen devices, serum total cholesterol, free proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) significantly decreased. Nonetheless, the patient developed a skin rash 2 weeks after the second injection and the lesion spontaneously resolved without any treatment approximately 1 month later. CONCLUSIONS: The effectiveness of proprotein convertase subtilisin/kexin type 9 monoclonal antibody seems to be stable after being stored under freeze-thaw conditions. However, improperly stored drugs should be discarded to avoid any potential undesirable side effects.

Cumulative incidence of and risk factors for herpes zoster among patients with diabetes mellitus: Results from a 10-year nested case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for herpes zoster (HZ). Data specific to the incidence of and risk factors for HZ among Thai DM patients are scarce. METHODS: This nested case-control study evaluated a 10-year cohort of DM patients (N = 1428) treated at Siriraj Hospital (Bangkok, Thailand). We included 40 cases with ≥1 episode of HZ, and we randomly sampled 175 non-HZ controls. Data were obtained from chart review and the ICD-10 diagnosis code, pharmacy database, and laboratory database. RESULTS: During 2005-2014, the cumulative incidence and incidence rate of HZ among all study patients was 2.80% [95%CI: 2.00-3.79%] and 3.96 [95%CI: 2.90-5.28] per 1000 person-years, respectively. The most common site was trunk (27.5%) followed by zoster ophthalmic (22.5%). Only 1 case required hospitalization. Independent risk factors for HZ included underlying hypertension [aOR: 3.48, 95%CI: 1.28-9.43; p = 0.01], number of hypoglycemic drugs used [aOR: 1.46, 95%CI: 1.03-2.08; p = 0.04], and previous herbal remedy use [aOR: 3.83, 95%CI: 1.06-13.84; p = 0.04]. Higher body mass index was a protective factor against HZ [aOR: 0.89, 95%CI: 0.81-0.98; p = 0.02]. CONCLUSION: The incidence of HZ among DM patients at our center is comparable to other Asian countries. The identified independent risk factors can be used to discern patients who would benefit most from preventive interventions.