Viral hepatitis B (hepatitis B) is a systemic infectious disease characterized by hepatitis and necrotic lesions, caused by hepatitis B virus (HBV) infection. Hepatitis B is a worldwide epidemic infectious disease with a high incidence, strong infectious force and serious harm to human health. At present, about 2 billion people in the world have been infected with hepatitis B virus, and about 90 million people in China are infected with hepatitis B virus, making it clear that China has become a major hepatitis B country [1]. Therefore, both the mainland and the world are in urgent need of safe and effective hepatitis B treatment drugs. Based on this clinical background, the new hepatitis B drug propofol tenofovir fumarate (TAF) has attracted much attention as soon as it has been listed, and some media have even called it "the strongest hepatitis B drug in history".
1. First-line commonly used drugs for the treatment of hepatitis B
At present, the drugs commonly used in the treatment of hepatitis B in China are: tenofovir disoproxil (TDF), entecavir, lamivudine, adefovir ester and so on. Tenofovir disoproxil is one of the drugs of choice for the treatment of chronic hepatitis B, with the most common adverse reactions being nausea, vomiting, diarrhea and bloating, chronic tubular injury, renal dysfunction and osteoporosis, possibly causing lactic acidosis and hepatomegaly associated with steatosis, and there have been case reports of switching to entecavir (ETV) therapy for Fanconi syndrome. The above-mentioned commonly used hepatitis B drugs have more and more serious adverse reactions in long-term use, and the listing of propofol tenofovir fumarate (TAF) has broken this situation, and TAF, which is known for its excellent safety and efficacy, will bring better choices to hepatitis B patients.
2. Introduction to propofol tenofovir fumarate (TAF).
Propofol tenofovir fumarate (alias: phosprofinovir) and tenofovir alafenamide tablets (TAF), chemical name: N-[(S)-[(1R)-2-(6-amino-9H-9-yl)-1-methylethoxy]methyl]phenoxyphosphinolyl]-1-methylethyl ester-(2E)-2-butenediate (2:1).
TAF is the only new drug approved by the FDA for the treatment of hepatitis B in the past 10 years. TAF is an upgraded version of TDF, TAF overcomes the shortcomings of some TDF, its safety and effectiveness are higher than TDF. Compared with TDF, TAF has stronger antiviral activity, and the required dose is very small, only 25 mg, which is about 1/12 of the TDF dose. TAF is 4 times higher than TDF intracellular drug concentrations and 90% lower plasma drug concentrations. A high cell concentration means that the drug is efficient, while a lower concentration in the blood plasma means that there are fewer adverse reactions. Clinical trials have also shown [2], TAF is no less effective than TDF, and is less toxic to the kidneys and bones, and more effective in entering lymphoid tissue. At the same time, TAF has been approved in combination with other drugs for the treatment of AIDS.
3. Research and development of propofol tenofovir fumarate (TAF) at home and abroad
Propofol tenofovir fumarate (trade name: Vemlidy) was developed by Gilead Sciences and approved for marketing by the U.S. Food and Drug Administration (FDA) in November 2016. It was approved for listing by the Japanese Medical Device Review and Approval Authority (PMDA) in December 2016 and by the European Medicines Agency (EMA) in January 2017. In May 2019, GILEAD completed import registration in the mainland, and TAF was approved for sale in the mainland as an original research drug. At present, a number of pharmaceutical companies in the mainland have developed propofol tenofovir fumarate tablets, among which the manufacturers that have obtained the registration acceptance number are: North China Pharmaceutical Huakun Hebei Biotechnology Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Jiangxi Qingfeng Pharmaceutical Co., Ltd. and many other companies.
4. Clinical study of propofol tenofovir fumarate (TAF).
In a cohort study of 108 Chinese mainland patients[3], participants had a mean age of 43 years, with 73% males and 45%, 1%, 51%, and 1% of the B, B/C, C, and D genotypes, respectively. Patients who were untreated and treated, hepatically compensated and HBeAg-negative were randomly divided into two groups in a 2:1 ratio, namely TAF (25 mg once daily) and tenofovir group (300 mg once daily). There were 104 subjects in the TAF group and 50 subjects in the tenofovir group.
Changes in bone density (BMD) in Chinese mainland patients: After 96 weeks of treatment, data from both sets of studies showed a small increase in the average percentage of spinal bone density and a small decrease in the mean percentage of hip bone density in the TAF group compared to baseline. The average percentage of bone mineral density decline in the spine and the average percentage of decreased bone density in the hip were higher in the tenofovir group compared to baseline and higher than in the TAF group.
Chinese mainland patients with changes in renal function indicators: after 96 weeks of treatment, data from both sets of studies showed that the renal function indicators of the TAF group were less variable than those in the tenofovir group. (There was less increase in serum creatinine in the TAF group compared with the tenofovir group; the median eGFR in the TAF group was less reduced than in the tenofovir group; the median value of the ratio of urine β2 microglobulin to creatinine in the TAF group was lower, while the median value in the tenofovir group was increased).)
In summary, clinical trial results have shown that TAF is an upgraded version of tenofovir, not only at a dosage of only 1/12 of tenofovir, but also with significantly fewer side effects [4].
5. Propofol tenofovir fumarate (TAF) is suitable for people
(1) Current guidelines recommend the preferred TAF for all patients with hepatitis B for initial treatment. The choice of TAF not only avoids the risk of drug resistance in the future, but also minimizes the cost of treatment and the risk of treatment.
(2) Patients who have previously been resistant to nucleoside monotherapy or have a poor drug response. If the response to entecavir is not good, the TAF can be replaced directly;
(3) Patients previously treated with lamivudine combined with adefovir or entecavir plus adefovir can be replaced by ATAF monotherapy.
(4) After lamivudine resistance, it can be changed to TAF treatment;
(5) Patients with renal insufficiency and osteoporosis using other hepatitis B drugs can use TAF.
6. Propofol tenofovir fumarate (TAF) usage and dosage
TAF should be taken under the guidance of a professional physician. Adults and adolescents (12 years and older, weighing at least 35 kg): 1 time / day, 1 tablet / time, orally with food. Missing dose: If the time of missing a dose of TAF does not exceed 18 hours, one dose should be taken as soon as possible and normal dosing time is restored; if the missed dose is more than 18 hours, it should not be supplemented after taking the drug, only the normal administration time should be restored.
7. Price and access to propofol tenofovir fumarate (TAF).
Over the past decade, TAF is the only new drug to treat hepatitis B that has been approved for marketing by the FDA. The self-proclaimed "best ever" anti-hepatitis B drug was approved for marketing in China in November 2019, allowing people with chronic hepatitis B in China to benefit from the world's latest drugs. The TAF is expensive, the initial price of TAF is 1180 yuan / bottle, 30 tablets / bottle, 25 mg / tablet. Then, after the national drug price negotiation and inclusion in medical insurance, TAF was reduced to 539 yuan / bottle in early 2020. According to statistics, the annual drug cost of TAF treatment is about 6500 yuan, and the burden is still not small after deducting the centralized part of medical insurance. Therefore, many patients choose to import generic drugs. Relatively speaking, the price of generic drugs reduces the consumption pressure of patients and the efficacy is reliable. Patients in need can be consulted and obtained through regular overseas medical institutions (such as medical companion travel).
8. Summary
TAF has a good effect on reducing serum HBV-DNA level, inhibiting HBV replication, and improving liver function in patients with chronic hepatitis B virus infection, and compared with TDF, it has the characteristics of low dosage, good efficacy, and few adverse reactions. Therefore, it can effectively improve the treatment effect of patients, delay the progression of the disease, and prolong the survival time. For patients aged >60 years, bone disease, and renal dysfunction, TAF is recommended as the drug of choice for the treatment of chronic hepatitis B. Many experts believe that in the next 10 years, there will be a big breakthrough in hepatitis B treatment, and anti-hepatitis B drugs, including TAF, will be further optimized and upgraded. I believe that with the joint efforts of scientists and clinicians, it is very promising to defeat hepatitis B, or to make hepatitis B no longer threaten human health!