Table 2.
Study characteristics.
| Author and Year | Induction and Maintenance IS Regimen | Regimen Doses/Duration | Comparison Regimen | Patients in AI Agent Arm, N | Total Patients, N | Duration of Follow-up (months) | Primary Outcomes | II Definition |
|---|---|---|---|---|---|---|---|---|
| Allotransplant | ||||||||
| ETA | ||||||||
| Hering 200511 | ATG, DAC, SIR, TAC (MMF substitution at 1y) | ETA 50mg IV 1h pre-txp, 25mg SQ on POD 3, 7, 10 | None | 8 | 8 | 12 | II, safety via severity and duration of procedural complications, infections, or adverse medication or islet events | FBG <126 mg/dL and 2h postprandial BG <180 after insulin discontinuation |
| Bellin 200812 | ATG, CsA, EVR (possible MPA substitution at 1y) | ETA 50mg IV 1h pre-txp, 24mg SQ on POD 3, 7, 10 | None | 6 | 6 | 24 | Safety via CBC, coagulation studies, hepatic panel, creatinine, 24h urine albumin excretion, GFR, medication levels | FBG <127 mg/dL and 2h postprandial BG <180 mg/dL without exogenous inuslin |
| Faradji 200810 | EP | ETA 50mg IV 1h pre-txp, 25mg SQ 2x/wk x 2wk | EP | 4 | 9 | 18 | II following supplemental islet cell infusion | C-peptide positivity without GDF without exogenous insulin |
| Froud 200813 | ATZ, SIR, TAC then SIR, MPA | ETA 50mg IV 1h pre-op, 25mg SQ 2x/wk x 2wk | EP | 3 | 19 | 24 | II, graft function, MMTT, IVGTT | NR |
| Gangemi 20088 | EP | ETA 50mg IV pre-txp, 25mg SQ on POD 3, 7, 10 | EP | 6 | 10 | 15 | II | Without exogenous insulin, FBG >140 mg/dL <4 times/wk and 2h postprandial BG >180 mg/dL <5 times/wk |
| Koh 201014 | DAC or ATG, TAC, SIR or MMF | ETA 50mg IV pre-txp, 25mg SQ on POD 3, 7, 10 | None | 17 | 17 | 19.8 ± 3.2 | II | HbA1c ≤7%, FBG >140 mg/dL <4 times/wk and 2-hr postprandial BG >180 mg/dL <4 times/wk |
| Rickels 20139 | ATG (BAS for 2nd infusion), SIR, TAC | ETA 50mg IV pre-txp, 25mg SQ on POD 3, 7, 10 | EP and normal controls | 11 | 27 | 24 | II, argTT | FBG ≤126 mg/dL and 90 min MMTT BG ≤180 mg/dL, s/p > 1 wk insulin taper |
| INF | ||||||||
| Froud 200515 | EP | INF 5 or 10mg/kg 2h pre-txp | EP | 8 | 16 | 18 | II | FBG <127 mg/dL without exogenous inuslin |
| ETA + ANA | ||||||||
| Matsumoto 201116 | ATG, TAC, MMF | ANA 100mg IV 1h pre-txp, then 100mg SQ daily x 7d; ETA 50mg IV 1h pre-txp, 25mg SQ on POD 3, 6, 10 | ETA + EP | 3 | 6 | 24 | Total insulin required, HbA1c, SUITO index (II defined as >26) | SUITO >26 |
| Takita 201217 | ATG, TAC, MMF | ANA 100mg IV 1h pre-txp then 100mg SQ daily x 7d; ETA 50mg IV 1h pre-txp then 25mg SQ on POD 3, 7, 10 | ETA + EP | 4 | 8 | 12 | Adverse events within 3 months | - |
| ETA Long-term Follow-up | ||||||||
| Bellin 201219 | ATG ± DAC (or TEP alone without ETA) | NR | ATG + TNF blocker; ATG without TNF blocker; IL-2Ra; pancreas transplant | 29 | 946 | 60 | II | No exogenous insulin use for ≥14 consecutive days |
| Qi 201420 | EP | ETA 50mg IV pre-txp, 25mg SQ on POD 3, 7, 10 | EP | 6 | 10 | 60 | II, C-peptide, HbA1c, MMTT, OGTT, IVGTT, GST, Ryan HYPO score | Without exogenous insulin, FBG >140 mg/dL <4 times/wk and 2h postprandial BG >180 mg/dL <5 times/wk |
| Autotransplant | ||||||||
| ETA or ETA + ANA | ||||||||
| Naziruddin 201818 | ATG (other agents NR) | ETA 50mg SQ on POD 0, 25mg SQ on POD 3, 7, 10; in ANA + ETA group, added ANA 100mg SQ daily POD 0–7 | No ETA or ANA (other agents NR) | ETA – 32; ANA + ETA – 59 | 100 | 12 | SUITO index, basal C-peptide, FBG, HbA1c, proinsulin, IL6, IL-8, MCP-1 | - |
Abbreviations: ANA, anakinra; AI, anti-inflammatory; argTT, intravenous arginine tolerance test; ATG, antithymocyte globulin; ATZ, alemtuzumab; BAS, basiliximab; BG, blood glucose; CBC, complete blood count; CsA, cyclosporine; DAC, daclizumab; EP, Edmonton Protocol (DAC, SIR, TAC); ETA, etanercept; EVR, everolimus; FBG, fasting blood glucose; GFR, glomerular filtration rate; GST, glucagon stimulation test; h, hour; HbA1c, hemoglobin A1c; IL-1Ra, interleukin-1 receptor antagonist; IL-6, interleukin-6; IL-8, interleukin-8; II, insulin independence; INF, infliximab; IS, immunosuppression; IV, intravenous; IVGTT, intravenous glucose tolerance test; MCP-1, monocyte chemoattractant protein 1; MMF, mycophenolate mofetil; MMTT, mixed meal tolerance test; MPA, mycophenolic acid; NR, not recorded; OGTT, oral glucose tolerance test; POD, post-operative day; SIR, sirolimus; SQ, subcutaneous; SUITO, secretory unit of islet transplant objects; TAC, tacrolimus; TEP, teplizumab; txp, transplant; y, year