Table 2.
IgG dose, IgG trough level and outcomes of Primary Immunodeficiency disease patients in included clinical studies.
| SN. | Studies | Type of IgG used | Dosing protocol, Mean(range) mg/Kg/week | IgG trough level (Mean ± SD) mg/dl | Severe infections n (rate/patient/year) | Overall infection (n, CI)-annual rate per patient | Days of hospitalization (n, Mean ± SD) | Days missed from work/school (n, Mean ± SD) | Adverse events/patient/year |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Aydiner 201529 | IVIG | 330–1250 mg/kg/wk | 976 ± 564 mg/dl | 0 | 7 events in 4 pts in 10 months | na | na | na |
| SCIG | 300–430 mg/kg/wk | 1025 ± 409 mg/dl | |||||||
| 2 | Berger 201030 | IVIG | 100–200 mg/kg/wk | 914.8 ± 273.37 mg/dl | 0.03 | 3.42 | na | 4.5/subject/year | 27.5 |
| 16% SCIG | 878 ± 234.77 mg/dl | ||||||||
| 3 | Ballow 201631 | IVIG | 300–800 mg/kg/wk | 800–1000 mg/dl | 1 episode | 0.051 | 0.2 ± 1.1 | 6.2 ± 17.7 | 20.2 |
| 5% IVIG | |||||||||
| 4 | Bezrodnik 20138 | IVIG | 556 mg/kg/month (420–870) | 960.2 mg/dl | 3 episodes in IVIG/1 in SCIG | 1.4 | 0 | na | na |
| 16% SCIG | 139 mg/kg/wk (105–181) | 1317 mg/dl (wk16), 1309.2 mg/dl (wk 24) and 1231.5 mg/dl (wk 36) | 0.4 | 0 | na | 0.14 | |||
| 5 | Bezrodnik 201432 | IVIG (48 weeks) | na | 1005.33 ± 419.420 mg/dl | 4 episodes | 2–7 | na | na | 0.13 |
| 16% SCIG (9 months) | 133 mg/kg/wk (100–192) | 1205 ± 457.990 mg/dl | 3 episodes | 1–2 | na | na | 0.02 | ||
| 6 | Borte 20179 | Period 1-IVIG 10% for 13 wk/SCIG 16% for 12 wks. | 125 ± 42 mg/kg/week (20% SCIG) | IVIG 10% = 720 mg/dl SCIG 16% = 897 mg/dl | 0 IVIG, 1(0.27) SCIG 16%) | 6.29 rate (IVIG), 8.92 rate (SCIG 16%), 4.38 (SCIG 20%) | 1 (0.12) IVIG,2 (0.54) SCIG 16% | 90 (10.69) IVIG/187(50.42) SCIG | 0.058 |
| Period 2-SCIG 20% for 52 wk | SCIG 20% = 827 mg/dl | 1(0.022) | 200(4.38) | 7(0.15)-SCIG | 710 (15.55) | ||||
| 7 | Borte 201710 | 10% IVIG (/3 weeks) | 485 mg/kg/month | 1100–1220 mg/dl | 3.68 (overall) 4.19 (3 weekly)) |
na | 37 absences (61.95%) | Serious AE 13% (4 weekly) vs. 5% in 4 weekly | |
| 10% IVIG (/4 weeks) | 810–870 mg/dl | 3.33 (4 weekly) | 1 (0.08) | 3.64 | |||||
| 8 | Borte 201133 | IVIG/SCIG | 200–800 mg/kg/wk | 694 mg/dl (c), 790 mg/dl (a), 781 mg/dl (ad) g/l | 0 | 4.77/5.18 (a)/5.47 (ad) | 8.36(c),0(a),0.63(ad) | 1.7 (c), na (a), na (ad) | 0.04(c),0.035 (a),0.08(ad)/infusion |
| 20% SCIG | 129.9 mg/kg/wk -children(c), 113.7 mg/kg/wk- adolescents (a) and 114.3 mg/kg/wk- adults (ad) |
786 mg/dl (c), 791 mg/dl (a), 831 mg/dl (ad) | 0 | ||||||
| 9 | Haddad 20126 | 20% SCIG (1:1) EU | 120 mg/kg/wk | 810 ± 144 mg/dl | 0 | 5.18 | 3.48 | 8 | 0.59 events/infusion (1:1) |
| 20% SCIG (1.5:1) USA | 210 mg/kg/wk | 1254 ± 322 mg/dl | 0 | 2.76 | 0.2 | 2.06 | 0.06 in 1:1 | ||
| 10 | Hagan 201011 | 20% SCIG | 179.6–224.3 mg/kg (IgPro20) | 1210–1290 mg/dl | 0 | 2.76 | 0.2 | 2.06 | local AE = 0.592, other than local AE = 0.043 |
| 11 | Jolles 201134 | IVIG | Pre study = 702 mg/dl | 1(wash out) = 0.03 events/patient/year | 5.18 | 3.48 | 8 | 0.177/infusion | |
| 20% SCIG | 120 ± 35.72 mg/kg/wk (20% SCIG) | On infusion = 809 mg/dl | |||||||
| 12 | Kanegane 201435 | IVIG | 77.3 ± 30.5 mg/kg/month | 653 ± 140 mg/dl (IVIG) | 0 | 2.98 | 0.55 | 3.48 | 0.461/infusion |
| 20% SCIG | 87.8 ± 35.2 mg/kg/wk SCIG | 715 ± 151 mg/dl (SCIG) | |||||||
| 13 | Krivan 201636 | IqYmune | 220–970 mg/kg | 579 ± 203 mg/dl | 1 (0.017) | 3.79 | 0.89 | 1.01 | 0.45/infusion |
| 773/- 236 mg/dk (IVIG) | |||||||||
| 14 | Melamed 201637 | IVIG 5% 21-day infusion | 300–800 mg/kg/wk | 21-day infusion = 987–1083 mg/dl | 2 (0.09) | 3.08 | 3.5 | 1.1 | 0.39/infusion |
| IVIG 5% 28-day infusion | 28-day infusion = 822–882 mg/dl | ||||||||
| 15 | Moy 201038 | IVIG 5% | 469.4 mg/kg/month (21-day infusion) 466.2 mg/kg/month (28-day infusion) |
21-day infusion = 936–1240 mg/dl | 0 | 3.07 | 2 days | 8.73 | 1 AE/3 infusions |
| 28-day infusion = 833–1140 mg/dl | |||||||||
| 16 | Patel 201539 | SCIG 20% | 674 mg/kg/wk (260–2000) 552 mg/kg/month (IVIG) |
794 mg/dl (on IVIG) and 943 mg/dl (IGSC 20%) | 0.03 | 0.067 rate | na | na | 41 (47%) local AEs |
| 17 | Quinti 201117 | IVIG | CVID- 398 ± 167 mg/kg/wk | CVID-667 ± 176 mg/dl | 0.06–0.1 episodes patient-year | na | na | na | na |
| XLA-608 ± 273 mg/kg/wk | XLA-758 ± 202 mg/dl | 0.03–0.11 episodes patient-year | |||||||
| 18 | Stein 201640 | 10% IVIG | 501.7 mg/kg/month | 923.9 mg/dl | 2 (0.04) | 2.9 | 0.6 | 2.8 | 44(98%)- 450 events |
| 19 | Suez 201641 | IVIG 10% and SCIG 20% | 222 ± 71 mg/kg/wk | 1523 mg/dl with IGSC and 1200 mg/dl in IVIG 10% in 3 weeks | 0 | 3.86 in IVIG | 0.02 | 1.16 | 0.036/infusion |
| 2.41 in SCIG | |||||||||
| 20 | Viallard 201742 | Tegeline | 442 mg/kg/month (286–608) | Tegeline 805 ± 134 mg/dl | Tegeline-0 | Tegeline-4.35 (0–21.8) | Tegeline-0 | Tegeline-8.8 (6.4–11.9) | Tegeline-0.09 |
| ClairYg | ClairYg 917 ± 172 mg/dl | ClairYg-0 | ClairYg-4.3(0–15.1) | ClairYg-0 | ClairYg-0.3(0.1–0.9) | ClairYg-0.08 | |||
| 21 | Vultaggio 201543 | IVIG | Maintenance of total monthly dose of historic IVIG split into four weekly doses of SCIG | Baseline 635 ± 242.8 mg/dl | 5 (0.056) | 33/39 patients (84.6%)- infection | 1.93 ± 4.08 (IVIG) | 15.27 ± 23.17 (IVIG) | Local reactions (14/50 = 28%) |
| SCIG 16% | 671 ± 217.5 mg/dl | 0.64 ± 2.94 (SCIG) | 2.26 ± 4.45 (SCIG) | ||||||
| 22 | Wasserman 201244 | IVIG 10% | 500 mg/kg/wk (254–1029) | 1076 ± 254 mg/dl (606–1780 mg/dl) in 21-days | 2 (0.035) | 2.6 (2.3–2.7) | 0.21 | 2.28 | 937 events |
| 943 ± 215 mg/dl (487–2250) in 28-days | |||||||||
| 23 | Wasserman 201245 | IVIG/SCIG + IGHy vs. IVIG/SCIG alone | IGHy at 75U/g IgG followed by IgG 10% at 155 mg/kg/wk | <12 yrs = 995 mg/dl, >12 yrs 1070 mg/dl | 2(0.025) | 2.97 (IGHy) 4.51 (IVIG) |
0.02 (IGHy) vs. 0.06 (IVIG) | 0.28 (IGHy) vs. 0.23 (IVIG) | local AE = 0.199/infusion (IGHy) vs. 0.011/infusion (IVIG) |
| <12 yrs = 963 mg/dl, >12 yrs = 1040 mg/dl | |||||||||
| 24 | Wasserman 20167 | SCIG + IGHy vs. SCIG | 155 ± 53 mg/kg/week | 1135 mg/dl (2 week), 1195 mg/dl(3week), 983 mg/dl (4 week) | 5 (0.03) | 2.99 | 0.12 | 5.75 | 10.68/subjects' year |
Legend: IgG- Immunoglobulin, n = number, SD- Standard Deviation, wk-week, yrs-years IVIG- Intravenous Immunoglobulin, SCIG- Subcutaneous Immunoglobulin, na-not available, EU = Europe, USA= United States of America, ITT- Intent to treat, PPK- per-protocol pharmacokinetic, CVID= Common variable immunodeficiency disease, XLA = X-linked agammaglobulinemia, IGHy-recombinant human hyaluronidase