Mr. A, who had been suffering from multidrug-resistant tuberculosis (MDR-TB) for more than 20 years, had a dream come true. He was able to resume treatment as an effective drug came out. He was cured within a year. The patient is in his mid-40s who was infected with MDR-TB at the age of 25. He could not have a social life struggling to fight the disease. However, now, he has a new life.

The patient A, who refused to reveal his name, considered himself a lucky guy. It was not just because he has escaped from the MDR-TB. He was fortunate because the drugs A took are no more applicable to other patients. It is unlikely that other MDR-TB patients will enjoy the same luck that went to the patient A.

MDR-TB cured in 20 years with Situro-Deltyba combo

Mr. A found hope after two new TB treatments arrived in the market – Situro, and Deltyba. MDR-TB is resistant to basic TB treatments – isoniazid and rifampin. Extensively drug-resistant TB (XDR-TB) is also resistant to anti-TB injections amikacin, kanamycin, and capreomycin. MDR- and EDR-TB patients have fewer options for treatments and require more prolonged treatment time.

The patient A discontinued treatment in 2009 because no medicine was effective. At the time, he was diagnosed with XDR-TB. Five years later, Situro and Deltyba won local approval in March and October in 2014 and received insurance benefit from 2015. Physicians caring for the patient A decided to apply the two drugs to A. After obtaining approval from the new TB drug review committee under the Korea Centers for Disease Control and Prevention, the medical staffs prescribed the two medicines to him in August last year. The patient A’s symptoms started to improve, and the infectivity of the TB bacterium disappeared. However, the patient needed an extension of the use of the medication for a complete cure.

The problem was that the health authorities had limited the period of the use of the two drugs to 24 weeks. The patient A was responsive to the two medicines in 20 years but had to continue the medication for more than 24 weeks. The approval conditions of the two drugs state that the government covers the drug expenses within 24 weeks, but the patient has to pay for the additional use of the drugs after the 24th week. The government has been supporting the entire cost for TB treatment through national health insurance from July 2016. As Situro and Deltyba cost 30 million won ($26,760) for a 24-week treatment, respectively, the patient A was willing to spend 60 million won together to end the 20 years of pain from MDR-TB.

The patient A’s doctor decided to do everything to help the patient. The doctor applied for “approval of the drug use over the approved duration without insurance coverage” to the Health Insurance Review and Assessment Service (HIRA) in January, after winning the nod from the Institutional Review Board at the medical institution. The HIRA notifies the application to the Ministry of Food and Drug Safety, receives opinions, and finally makes a decision on approval or disapproval. During the application process, the patient can use the drugs off-label.

The doctor also submitted overseas cases that treated MDR-TB by using Situro and Deltyba for more than 24 weeks and related guidelines as backup data. EndTB, a group of European TB researchers from 17 countries around the world, said in guidelines for new TB medicines that the most common misconception among physicians was that they could use Situro and Deltyba for 24 weeks only. "These drugs should be used at least 24 weeks and can be used for 18 to 24 months in total," it said.

Authorities disapprove the off-label use of Situro-Deltyba combo

However, the food and drug safety ministry did not agree with EndTB researchers. The ministry informed the HIRA that it did not find medical ground for the prescription of more than 24 weeks of Situro and Delbyta. It meant that even if the patient wanted to pay the full expenses, the patient was not allowed to use the drug for more than 24 weeks.

"We have reviewed documents regarding the use of the two drugs for more than 24 weeks. Some documents used Situro and Deltyba in combination with other drugs for more than 24 weeks. However, there was no basis for the case of using the two together for more than 24 weeks,” said an official at the food and drug safety ministry’s drug evaluation and coordination department.

Notified by the ministry, the HIRA announced on Aug. 1 that the government disapproved the use of the two drugs more than the approved period without insurance coverage.

‘Government ignored expert opinions’

TB experts criticized the government’s decision for killing the possibility to treat MDR-TB.

“The request was not about demanding approval conditions. It was an expert’s opinion to allow the patient to pay the full expenses for the medication for the exceeding part of the treatment. However, the government did not allow it,” said Shim Tae-seon, a professor of respiratory medicine at Asan Medical Center. Shim also serves as head of the KCDC’s review committee for new TB drugs.

According to Shim, the use of new TB treatments is increasingly extended to non-licensed indications such as extracranial TB and pediatric patients. “The use of the new drugs is also extending to more than 24 weeks. It may be difficult to change the approval conditions to allow the use for more than 24 weeks based on a new, phase-3 study. However, the government should enable the drug use over 24 weeks under the consultation with medical experts,” he said.

Another said the government was blocking treatment for MDR-TB.

“The doctor had consultations with the patient, earned the consent to use the new medicines, and saw good clinical results. Belatedly, however, the government said no,” said Im Jae-jun, a professor of the respiratory medicine at Seoul National University Hospital. “In other countries, doctors are already using them for over 24 weeks, but the Korean government is hampering it. Korean patients cannot enjoy the benefits of medical advancement.”

soo331@docdocdoc.co.kr

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