Table 3.

Exclusion criteria.

1.Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial.
2.Other current immunosuppressive treatments with biologicals or Disease Modifying Anti-Rheumatic Drugs (DMARDs) other than corticosteroids ≤20 mg/day or abatacept. Between treatment with other biologicals or DMARDs and start of abatacept trial treatment the wash out period of the pretreatment must be kept. In case of pre-treatment with rituximab, therapy must be stopped at least 6 months before inclusion to trial.
3.Treatment with systemic steroids (prednisolon) in daily dose >20 mg/day.
4.Active Hepatitis B or tuberculosis infection. For tuberculosis, Quantiferon test is gold standard. In case of a positive Quantiferon test, an active infection has to be excluded by 3 sputum and 3 gastric juice samples, assessed by microscopy, polymerase chain reaction (PCR) and culture. Chest X-ray recommended.
5.Active infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days prior to baseline.
6.Chronic infection requiring hospitalization or treatment with i.v. antibiotics within 30 days prior to baseline (does not apply for patients already pretreated with abatacept)
7.Acute bacterial or viral infection (patients with a chronic and clinically controlled infection can be included).
8.Patient on antiviral CMV prophylaxis within 28 days prior to baseline visit.
9.Any malignancies within the last 4 years with the exception of basal cell carcinoma and precancerous conditions (does not apply for patients already pre-treated with abatacept).
10.Current or planned pregnancy, nursing period.
11.EBV load of >5.000 IU/ml or CMV load of >1.000 IU/ml in plasma at screening.
12.Receipt of a live virus vaccine within 3 months prior to first application of trial medication.
13.Serious uncontrolled concomitant disease not caused by CTLA-4 insufficiency or LRBA deficiency.
14.Known human immunodeficiency virus (HIV) infection, infectious hepatitis (type A or C) or another uncontrolled infection.
15.Prior HSCT or HSCT planned within next 12 months.
16.Known hypersensitivity to the active substances or any of the excipients.
17.Participation in any other interventional clinical trial within the last 30 days before the start of this trial.
18.Simultaneous participation in other interventional trials; simultaneous participation in registry and diagnostic trials is allowed.
19.Known or persistent abuse of medication, drugs or alcohol.
20.Person who is in a relationship of dependence/employment with the sponsor or the investigator.
21.For women of child bearing potential: Failure to use during treatment with abatacept and at least up to 14 weeks after the last dose of abatacept one of the following safe contraceptive methods that can achieve a failure rate of less than 1% per year. Such methods include: (1) combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), (2) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), (3) intra-uterine device, (4) intrauterine hormone-releasing system (CTFG recommendations, 2014) [29].