Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB
Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB
Multidrug-resistant tuberculosis (MDR-TB) has emerged as a challenge worldwide. Few studies
 have prospectively reported outcomes in patients with pulmonary MDR-TB treated with
 adjunctive immunotherapy combined to standard chemotherapy. We aimed to assess whether
 immunotherapy with Interleukin(IL)-2 enhanced the clinical and immune effects of treatment on
 MDR-TB patients.We performed a multicentre prospective cohort study extend all over Jiangsu
 province in China. Two groups were generated based on the adjunctive rhIL-2 therapy during 24
 months regiman. Bacteriological and imaging data were followed during 24 months with cure
 rates analysed.
IL-2 therapy regimans are expected to restore the immune response or to change the
 immunologic status,thus allowing the host to more efficiently contain and eradicate immune
 responses, primarily those against cancers and infectious diseases.To address this, we
 performed a prospective randomized controlled multicenter cohort study of 8-month adjunctive
 immunotherapy with rhIL-2 for MDR-TB patients compared with the standard chemotherapy.

 This multicenter prospective clinical study was conducted at 13 tuberculosis centers
 (coordinating hospital specialized in tuberculosis) across Jiangsu province, China. Joined by
 the network system of The First Affiliated Hospital of Nanjing Medical University and CDC of
 Jiangsu province, participants were enrolled from 2009 to 2018. This study protocol was
 approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical
 University and was performed adhering to the ethical principles of the Declaration of
 Helsinki. All patients provided written informed consent before enrollment. The independent
 data and safety of the study were monitored by the hospital monitoring committee.

 Patients enrollment

 Eligible MDR-TB participants were identified by triplicate-spot sputum smears that were
 positive for acid-fast bacilli and a positive sputum culture with resistance to both
 isoniazid and rifampin, as determined by susceptibility tests and rapid screening tests . The
 results of these assays were confirmed using an L-G medium base modified in the Jiangsu
 province Centers for Disease Control and Prevention（CDC）.

 Treatment plan for the two cohorts: The patients in rhIL-2 group were given consisted of four
 courses of low-dose rhIL-2 (500，000 U/m) given subcutaneously (SC) once every other day
 (q.o.d.) for 30 days. Four courses were carried out separately during months 1, 3, 5, and 7.
 All enrolled patients with pulmonary MDR-TB received a 24-month standard anti-MDR-TB
 chemotherapy regimen:6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase
 treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase
 treatment.

 (Z: Pyrazinamide; KM: Kanamycin; AM: Amikacin; CM: Capreomycin; LFX: Levofloxacin; PTO:
 Prothionamide; PAS: Para-aminosalicylicacid; Pa:Pasiniazid); After finishing treatment
 regimen patients were followed up for a minimum of 36- months or until discontinuation of
 regimen, withdrawal of consent, loss to follow-up, death, or end of study.

 For all of the participants demographic measurements were recorded on the first clinical
 visit. Patient data were collected at enrollment and quarterly intervals. Sputum smear
 conversion, sputum culture conversion and chest CT scan improvement were followed up at 3, 6,
 12, 18, and 24 months for bacteriological and imaging data collected. Cure rates analysed and
 compared in both groups.

 The proportions of MDR-TB patients in the two groups achieving sputum smear/culture
 conversion, lung lesions absorption were assessed and compared.

 Safety assessment included clinical symptom observation, Incidences of adverse event （AE ）in
 two groups were assessed and compared. blood routine test, hematologic profile, blood
 biochemical examination including hepatic aminotransferase and blood ureantrogen/creatinine,
 blood electrolyte test (potassium, magnesium, calcium), serum thyroid stimulating
 hormone(TSH), audiology examinations, visual field and color examination.

 Cure rate was defined as first outcome. Sputum conversion rate was defined as second outcome.
Inclusion Criteria:

 Patients had/were:

 1. a confirmed case of MDR-TB;

 2. aged 18-70 years old;

 3. a chest CT showing visible lung lesions, with or without holes;

 4. a fasting plasma glucose of less than 7.8 mol/L and a normal fundus examination, if
 they were diabetic;

 5. voluntarily joined this study and signed an informed consent form.

 Exclusion Criteria:

 1. two or more total allergies or any drug or food allergies;

 2. resistant to some drugs of this program;

 3. severe disorders of liver, kidney, or hematologic system functions;

 4. any metabolic diseases, autoimmune diseases, endocrine diseases, cancer, or HIV/AIDS;

 5. a long-term use of immunosuppressive agents;

 6. a blood system dysfunction;

 7. a history of mental illness or epilepsy;

 8. pregnant or lactating;

 9. participated in another clinical trial in the last 3 months or were currently
 participating in other ongoing clinical trials;

 10. long-term alcohol abuse>10 years and more than two alcoholic drinks per day);

 11. any other factor rendering them unsuitable to participate in this project, such as a
 history of unreliability.