The BPaL regimen offers hope to more
drug-resistant TB patients in the Philippines

The BPaL operational research (OR) in the Philippines achieved a major milestone as it opened its door to the first enrollee last May 2021.  With implementation activities rolled-out and intensified through the dedicated initiative and able guidance of the Research Team led by Dr Irene Flores (Principal Investigator) and support from partners, the study has enrolled an additional seven patients from two OR sites as of August 2021.  Please find article on the first patient in this link: The Philippines Enrols First Patient With Highly Drug-Resistant TB On The BPal Regimen.

The OR’s second patient is a 36 year-old female from Nueva Ecija who was enrolled in June 2021 in Jose B Lingad Memorial General Hospital (JBLMGH).  She started to have “dry cough” for more than 2 weeks with weight l

oss and loss of appetite and was initially diagnosed with pneumonia in February confirmed by chest x-ray. GeneXpert results confirmed her as rifampicin-resistant or RR-TB. After 25 days on the shorter all-oral bedaquiline-containing regimen (SSOR), she experienced gastrointestinal complaints unrelieved by ancillary medicines and split dosing of anti-TB medications. She was referred to the TB Medical Advisory Committee (TBMAC) who suggested enrolment to the BPaL OR in JBLMGH.   She is currently on her 3^rd month of treatment, and attests to the favourable effect of the regimen saying “Maayos po ang pakiramdam ko at gumana nang kumain” [“I feel well and I now have good appetite.”], with her weight gain as a further testament to her improvement.

The third patient is a 17 year-old female from Magalang, Pampanga, initially diagnosed with diabetes in 2017 followed by the diagnosis of RR-TB through GeneXpert. She started her treatment in July 2019 on the standardized injectable-based shorter regimen (SSTR) and completed her treatment in April 2020; however, with positive cultures at the 8^th and 9^th months of treatment and even on the 6^th month post-treatment.  Her treatment failure was attributed to uncontrolled diabetes. Upon referral to the regional TBMAC in May 2021, she was immediately identified as a possible BPaL patient. Because of her age, there was a concern regarding enrolment. However, countering this concern, and with the approval of the TB MAC, she eagerly 

agreed to be enrolled in the BPaL OR stating, “Mas ok po kung mas maikli at mas konti ang gamutan, basta wala rin pong injection” [“The shorter the duration, and the lesser medicines, the better, as long as there is no injection.’]. She was enrolled last June 24, 2021 also in JBLMGH and now already on her 3^rd month of treatment without experiencing adverse events except for transient palpitations on the third day of treatment.

Also from JBLMGH, the fourth patient is a 47 year-old female, who is already on her 4^th regimen for TB. She was first diagnosed with pulmonary TB in 2018 in Bulacan and was subsequently treated for MDR-TB on SSTR. After 2 months of treatment, the patient was lost to follow-up (LFTU) because she could no longer endure the pain of the daily injections. She eventually returned to treatment and completed 6 months; however, her condition continued to progress; hence was enrolled to SSOR.  She was referred to TBMAC in early June 2021 and the committee decided to enrol the patient under the BPaL OR. She also has diabetes type 2 for 15 years. Family history revealed that the patient’s mother, who also had diabetes, died of PTB about 10 years ago.  She is presently on her 3^rd month of treatment. Because of anemia on the 2^nd month, linezolid was adjusted to 600mg OD.

Ilocos Training and Research Medical Center (ITRMC) enrolled its first patient in June 2021 making him the fifth patient for the OR.  He is a 47 year-old male patient, who is currently on his 3^rd month of the BPaL regimen. He was diagnosed with RR-TB after an outcome of loss to follow-up from his previous DS-TB treatment. He was referred to ITRMC for the MDR-TB treatment under SSOR; however, after 25 days, the patient developed intolerance to the medicines. Because of this, the RTBMAC recommended enrolment to the BPaL OR.  The regimen is well tolerated by the patient.

The sixth patient is a 23 year old male from Batangas with previous treatment of DS-TB in Jan 2020. He manifested with hepatic encephalopathy while on the He had DS-TB medication; hence his regimen was shifted to the longer regimen for fluoroquinolone-susceptible (SLOR FQS). He again developed an increase in transaminases. De-challenge and re-challenge pointed to levofloxacin as the culprit of the adverse event; hence, together with his family, they agreed to take the BPaL regimen where lesser number of drugs are administered. He was enrolled in July 2021.

Eversley Child Sanitarium and General Hospital (ECSGH) enrolled its very first patient in July 2021 making him the seventh patient to be enrolled to the OR.  He is a 64 year-old male from Danao with a history of treatment failure to the DS-TB regimen.  He was later diagnosed with RRTB and underwent treatment at ECS PMDT Center where he was enrolled on the injectable-based shorter regimen. After 17 doses, he was lost to follow-up due to adverse events. He eventually returned to ECS for treatment. After 4 months, he was again lost to follow up due to uncontrolled comorbidities (diabetes and hypertension) and adverse events.  He again returned to the center where Line Probe Assay (LPA) test last July 15, 2021 yielded a result of FQ resistance. He had poorly controlled diabetes and hypertension at the time of screening. He is now on his 1st month of treatment under the BPaL regimen.

The eighth patient to the BPaL OR is a 36 year-old male who completed DSTB treatment with a “Cured” outcome in October 2017. He claimed to be asymptomatic until about 3 months prior to his diagnosis of MDR-TB. He was started on SSOR last July 27,2021. The regimen was well tolerated by the patient however his LPA result was positive for FQR. He was immediately referred to JBLMGH and TBMAC for enrollment under the BPaL OR.  He is currently on his 1^st month of treatment.

A summary of the aforementioned patients’ information is provided below for quick reference.

 

Table 1.  Profile of enrollees’ treatment history and eligibility to BPaL OR

Enrolled patients			Eligibility for screening	Treatment history	Comorbidities and baseline findings	(Rif and) Fq DST
OR site	Patient	Age /Sex
JBLMGH	1	37F	FQ-Resistant	LTFU SSTR, 5months	DM 2, Pulmonary Hypertension; right-sided heart failure	FQR
JBLMGH	2	36F	Intolerance to SSOR (nausea & vomiting)	No previous DSTB treatment, On SSOR (26days prior to shift to BPaL OR	Subclinical hyperthyroidism (transient)	MTB Not detected
JBLMGH	3	17/F	Non-response to treatment	Treatment Failure to SSTR- 9months	DM type 1 on Humulin	FQ Susceptible
JBLMGH	4	47F	Non-response to treatment	Treatment Failure to SSTR- 11months	DM type 2, on Humulin	FQ Susceptible
ITRMC	5	47M	Intolerance to SSOR (nausea & vomiting)	Treatment after failure sec to Intolerance	None	FQ Susceptible
JBLMGH	6	23M	Intolerance to SSOR, (hypersentivity reaction,	LTFU -due to hepatic encephalopathy and transaminitis	None	FQ/SLI Indeterminate
ECSGH	7	64M	FQ-resistant	LTFU- -SSTR (17 doses) due to ADR; LTFU 2018- due to work	DM on Humulin Clinically blind left eye sec to trauma;	FQR
JBLMGH	8	36M	FQ-resistant	Previous DSTB (Cured) SSOR then shifted to BPaL due to LPA result	Alcoholism	FQR

 

It is hoped that this article will serve as a reference and provide insights to implementers, especially the OR site staff, as they screen patients for the BPaL regimen in their respective facilities.

The BPaL OR is a multi-country operational research which aims to determine the effectiveness and safety of the new novel treatment for MDR-TB in the country. The BPaL regimen is composed of three all-oral agents, bedaquiline, pretomanid and linezolid given for 6 months. The study targets to enrol 100 patients within two years of implementation.

 

(Appreciation is extended to Dr Irene Flores and members of the Research Team for providing the above patient information and photos for this article).