Characteristics of patients with SLE on AZA who were pregnant or trying to conceive at the time of 6-mercaptopurine metabolite level monitoring
| Case | Conception status | Prior lupus nephritis | AZA dose (mg/kg/day) | Metabolite levels (pmol/8×108 RBC) | Disease activity at time of metabolite measurement | Pregnancy outcome | Metabolite levels interpretation | Action based on therapeutic drug monitoring | |
| 6-TG | 6-MMP | ||||||||
| 1 | Preconception | Yes | 2.6 | 141 (low) | 5899 (elevated) | LLDAS | Not applicable | ‘Shunter’* | Switched to tacrolimus |
| 2.6 | 129 (low) | 5888 (elevated) | LLDAS | ||||||
| 2 | Preconception | Yes | 1.9 | Not detectable | Not detectable | LLDAS | Not applicable | Non-adherence† | Adherence discussion |
| 3 | Pregnant | No | 1.2 | 109 (low) | 384 | No LLDAS | Pre-eclampsia and preterm birth | Subtherapeutic dosing‡ | Dose increased |
| 1.8 | 207 (low) | 3361 | LLDAS | ||||||
| 2.1 | Not detectable | Not detectable | LLDAS | Non-adherence | Adherence discussion | ||||
| 4 | Preconception | Yes | 2.3 | 330 (normal) | 3019 | LLDAS | Not applicable | Therapeutic dosing | Continued same dose |
| 5 | Pregnant | Yes | 2.5 | 44 (low) | 269 | LLDAS | Uncomplicated term pregnancy | Non-adherence versus subtherapeutic dosing | Adherence discussion |
| 6 | Pregnant | Yes | 1.5 | 155 (low) | 3392 | LLDAS | Uncomplicated term pregnancy | Subtherapeutic dosing | Discussion about dose increase (patient refused) |
*Shunter: 6-MMP to 6-TG ratio ≥20 with high 6-MMP.
†Non-adherence: not detectable or barely detectable metabolite levels (ie, up to twice the minimal detectable 6-TG levels which is 30 pmol/8×108 RBC) despite adequate AZA dosing.
‡Subtherapeutic dosing: 6-TG levels <235 pmol/8×108 RBC while receiving a dose of AZA <2.0 mg/kg.
§Reference range for metabolites levels: 6-TG concentrations between 235 and 450 pmol/8×108 RBCs and 6-MMP levels <5700 pmol/8×108 RBC; LLDAS: as per previously validated definition: (1) SLEDAI-2K ≤4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI physician global assessment (scale 0–3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg/day and (5) well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
AZA, azathioprine; LLDAS, lupus low disease activity state; 6-MMP, 6-methylmercaptopurine; RBC, red blood cells; SLEDAI, SLE Disease Activity Index; 6-TG, 6-thioguanine.