1. Subcutaneous abatacept compassionate use program: South African real-world data provides further insight into the safety of subcutaneous abatacept in a TB endemic environment
IC Louw,1 M Ally,2 DC Janse van Rensburg,2 E Van Duuren,3 D Nel,3 H Miller-Janson,4 M de Necker,4 JC de Beer,4 H Duvenhage5 , J Elliott⁵
1Panorama Medical Centre, Cape Town, South Africa; 2University of Pretoria, Pretoria, South Africa; 3Jacaranda Hospital, Pretoria, South Africa; 4HEXOR (PTY) Ltd, Pretoria, South Africa; 5Bristol-Myers Squibb, Johannesburg, South Africa

2. Background
South Africa is a tuberculosis (TB) endemic country with the highest infection rate in the world; cases per population per year.¹
Screening for latent TB infection (LTBI) and treatment of any positive patient has reduced reactivation, however the chance of acquired TB infection remains high.
Therefore the use of a biologic therapy with a lower risk of TB infection is a high priority.
1. WHO Global tuberculosis report 2016
LTBI=latent tuberculosis infection; TB=tuberculosis

3. Best estimate of TB incidence rate in six developing countries

4. Background
In 2015 SARAA developed recommendations for the use of biologic DMARDS (bDMARDS) in South Africa with regards to TB.²
These recommendations address latent TB infection detection, treatment of LTBI and acquired TB.
They stratify the risk of TB exposure of the patient to facilitate decision- making on the appropriate choice of bDMARD, and further steps to prevent TB infection.
2 SARAA TB Recommendations

5. Recommendations for the use of biologic DMARDs in South Africa with regards to Tuberculosis
Latent TB infection
Regardless of the underlying rheumatic condition or choice of biologic DMARD (bDMARD), all prospective b-DMARD users must be screened for latent TB infection (LTBI).
2. LTBI should be tested by means of a PPD (Tuberculin Skin Test: TST); Induration of > or =5mm is regarded as a positive TST, irrespective of a previous Mantoux.
3. The IGRA test may be done as an additional test at the same time as the PPD.
4. A CXR is mandatory to exclude signs of LTBI such as apical scarring and granulomas or other suspicious abnormalities, and to rule out active TB.

6. SARAA TB Guidelines cont.
Treatment of LTBI
LTBI may be treated with either 9 months of isoniazid (INH) 300 mg/daily, or isoniazid 300mg/daily and rifampicin 600mg/d for 3 months. Biologic therapy may be commenced 1 month after LTB treatment is initiated.
2. Supplementation with 25mg Pyridoxine daily when INH is used.
3. Repetition of the LTBI course may be necessary if a patient has been exposed to TB or if their exposure risk has changed, irrespective of LTBI tests.

7. SARAA TB Guidelines cont.
Acquired TB
1. Stratify the risk of TB exposure of the patient to decide on the appropriate choice of a bDMARD and further steps to prevent TB infection.
2. The risk of TB is higher in the following settings:
a) Close contact with known or suspected TB cases.
b) Persons resident in an area with a high TB incidence, or a person who works or spends a significant amount of time in such an area.
c) Residents or employees of congregate settings such as correctional facilities, care facilities, shelters, schools, universities and colleges especially where there is poor ventilation.
d) Health care workers
e) Drug or alcohol abusers
f) Persons reliant on public transport such as taxis, buses and trains.

8. Recommendations for use of bDMARDs in patients with high TB risk in specific diseases
Rheumatoid arthritis
1. A non-TNF inhibitor biologic agent should be considered.
2. If a TNF inhibitor is used the following is recommended:
a) Isoniazid prophylaxis for the duration of the TNF inhibitor therapy
b) Regular clinical evaluation, followed by radiological and sputum analysis if required. c) Note that IGRA and TST is not to be used to evaluate patients with suspected
active TB
d) Education must be given to patients at high risk of TB regarding early symptoms of the disease and minimising the risk of TB exposure. Half of the TB cases on bDMARDs are extra-pulmonary and early symptoms may be non-specific.
e) Treatment decisions must be a shared process between the patient and the rheumatologist.
3. If a patient switches from a high risk for TB biologic to a low risk agent, vigilance for TB must remain high for the duration of biologic therapy.
4. Vigilance for TB must continue for at least 6 months after discontinuation of a bDMARD

9. Recommendations for use of bDMARDs in patients with high TB risk in specific diseases
Optimal course of action in suspected reactivation or acquired TB cases
1. Do CXR and sputum PCR for MTB, as well as further evaluation for extrapulmonary disease.
2. If TB not confirmed, involve a multidisciplinary team in order to expedite the diagnosis.
3. Low dose corticosteroids ≤10mg/d as well as conventional DMARDs may be used for the control of arthritis during TB treatment.
4. Recommencement of a biologic therapy should be done in consultation with the multidisciplinary team.
5. A safer biologic should be chosen if possible.

10. Objective
The primary objective was to gather information on the retention and safety of SC abatacept in the South African compassionate use programme (CUP), over a 30 month period, in a TB endemic environment.³
IC Louw, Ally N, Janse van Rensburg DC et al. Retention of use and safety of sc abatacept in RA: a patient record assessment in CUP in SA a TB endemic country ACR 2016 Abstract 2628

11. Methods
In June 2013, a CUP for rheumatoid arthritis patients who had completed long-term extension phases of clinical trials using SC abatacept 125mg/week was introduced.³
Demographic, safety and clinical data were retrospectively collected from patient records of 50 patients receiving regular follow up during the CUP (June 2013 to December 2015).³
CUP=Compassionate Use Programme
IC Louw et al. ACR 2016

12. Results
50 patients completed the CUP. Eighty-six percent of patients (n=43) were still on SC abatacept at the end of 30 months.
Ten percent of all patients (n=5) experienced an adverse event during the CUP.
No TB cases were recorded and general infections were recorded in 4%.
The SARAA TB guidelines provide a practical approach in patients who are at risk of acquiring TB in an endemic country.
These guidelines could also be of value to the other 5 seriously burdened countries namely: India, Indonesia, China, Nigeria and Pakistan. These countries, including SA, accounted for 60% of new TB cases in 2015.⁴
4 WHO Executive summary of TB

13. Results
RA drugs
Patients who used RA drugs n=50 (%)
Patients currently using RA drugs n=50 (%)
Arava
1 (2%)
0 (0%)
Chloroquine
14 (28%)
5 (10%)
Oral Corticosteroid
25 (50%)
20 (40%)
Parenteral Corticosteroid
Methotrexate
50 (100%)
48 (96%)
Salazopyrine
16 (32%)
3 (6%)
A summary of the medication that was used by patients for treating rheumatoid arthritis, before or during the CUP. From the total of 50 patients, column two refers to the number of patients who ever used any drugs for rheumatoid arthritis. Column three indicates the number and proportion of patients who, during the data collection period, were still using a drug for rheumatoid arthritis. The last column indicates the percentage of patients who, during the data collection period, were still using RA drugs, with the denominator being the number of patients who ever used a drug for rheumatoid arthritis, meaning that patients who have never used that specific drug, will be excluded from the calculation.
4 WHO Executive summary of TB

14. Conclusion
This South African real-world data demonstrates that SC abatacept is a well-tolerated and safer treatment option for patients with RA
This supports the practical implementation of the local SARAA recommendations in a TB endemic country

15. References WHO: Global Tuberculosis Report 2016. www.who.int/tb/data
SARAA TB Recommendations
Louw I Ally M, Janse van Rensburg DC et al. Retention of use and safety of subcutaneous abatacept in rheumatoid arthritis: a patient record assessment in a compassionate use programme in South Africa, a tuberculosis endemic country ACR annual meeting abstract no 2628
WHO: executive summary of TB