Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
3,824
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
0
Comments
0
Likes
7

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide
  • Ivig 0.7 g/kgMP 15mg/kg/d (1g/d)

Transcript

  • 1. Boonthorn 5 March 2010
  • 2.  Properties  Mode of action  Indication  FDA approved  Off-label used  Mode of administration  Adverse effect
  • 3.  Plasma fractionation (first step) by cold ethanol/Cohn–Oncley modification (fraction II)  98% IgG; > 90% monomeric IgG  Traces of other Ig e.g., IgA , IgM, and serum proteins  Addition of sugar, amino acids, or albumin stabilizes IgG from aggregation  Intact Fc receptor important for biological function  Opsonization and phagocytosis  Complement activation  Antibody-dependent cytotoxicity  Normal HL comparable to serum IgG  Normal proportion of IgG subclasses  Broad spectrum of Abs to bacterial and viral agents Mark Ballow et al, clinical immunology clinical and practice , third edition.
  • 4.  Donor selection  Donor screening  Donor plasma testing  Viral antibody screen ( HBsAg, anti HCV, anti – HIV )  Nucleic acid testing (NAT) : PCR ( HCV RNA,HBV DNA,HIV RNA, Parvovirus B19 DNA )  Donor deferrala  Mini-pool testing by NAT  Viral inactivationb  Depth filtration  Column chromatography  Caprylate precipitation  Low pH incubation  Solvent/detergent treatment  Nanofiltration  Pasteurization  PEG precipitation  a Plasma from donor is held for 6 months until donor returns for second plasmapheresis donation. b Not all products use same virus inactivation/removal steps. Each product uses 2–5 steps Mark Ballow et al, clinical immunology clinical and practice , third edition.
  • 5. ( HCV ) Clinical Reviews in Allergy & Immunology Volume 29, 2005
  • 6. Clinical Reviews in Allergy & Immunology Volume 29, 2005
  • 7. Clinical Reviews in Allergy & Immunology Volume 29, 2005
  • 8. Clinical Reviews in Allergy & Immunology Volume 29, 2005
  • 9. Mark Ballow et al, clinical immunology clinical and practice , third edition.
  • 10.  Anti-idiotypes against membrane-bound B-cell receptors ( for proliferation )  Fc-mediated inhibition of Ab production of B cells  Anti-CD 5 Ab directed against subset of B cells  Interference with differentiation of B cells ( neutralized BAFF )  Inhibition of IL-6 production that is required for Ab secretion by plasma cells  Induction of apoptosis of B cells  Neutralization of auto-Ab by anti-idiotypes (autoAb directed against factor VIII, DNA, intrinsic factor, thyroglobulin and ANCA )  Increased catabolisms of Ab via intracellular FcRn J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 11.  Binding of complement component C1  Binding of complement component C3b ,C4b  Binding of anaphylatoxins C3a and C5a  Increased degradation of C3b  Represent major mechanism in treatment of dermatomyositis, ( include GBS ) J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 12. Transplantation • Volume 88, Number 1, July 15, 2009
  • 13.  Affects differentiation,maturation and functional status of DC (inhibition , in vitro)  down-regulation of expression of co- stimulatory molecules  impairing ability of mature DC to produce IL-12  Enhancing ability to produce Il-10  inhibitionof auto- and alloreactive T-cell activation and proliferation  Modulates production of several cytokines (including IL-1, -2, -3, -4, -5, -10, TNF-α, and GM-CSF) and cytokine antagonists (IL-1RA) by monocyte-macrophages and lymphocytes Acta Derm Venereol 2007; 87: 206–218
  • 14.  Ab against TCR- β-chain, CD4 and CD8,Soluble CD4/CD8,HLA may inactivate auto-reactive T cell by compete and interrupt interaction with APCs  Ab against HLA molecules, superantigens  Ab against chemokine receptor CCR5  Inhibition of maturation of DC with consecutive  inhibition of T cell activation and induced apoptosis  Increase expression of TGF-β, IL-10, Fox P3 and enhance property of Treg J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 15.  Modulation of expression of adhesion molecules like ICAM  Antibodies against integrins  Antibodies against RGD (Arg-Gly-Asp )motif  Antibodies against CCR5 J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 16.  bind to several distinct epitopes on extra cellular portion of Fas and occurring anti-Fas Ab ( activation or functional blockade of death receptor depend on cell type concerned )  protect keratinocytes, target cell in TEN, from apoptosis via blockade of Fas death receptor  capable of promoting apoptosis in some lymphocytes and monocytes ,terminate immune reaction  inhibit TNFα-mediated cytotoxicity J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 17.  Complement  IVIg bind complement C1q, C3b and C4  C3b degradation is faster  Phagocytosis ( major mechanism of IVIg in ITP )  Blockade of Fc receptors (saturation of Fc receptors leads to decreased cellular destruction)  Induction of expression of inhibitory FcγIIB receptor  Cytokines  Inhibition of B cells  Induction of cytokine secretion and NO production  IgG metabolism  Blockade of protective intracellular FcRn J Neurol (2006) 253 [Suppl 5]: V/18–V/24
  • 18. Transplantation • Volume 88, Number 1, July 15, 2009
  • 19. NEJM 1999.
  • 20. No. of FDA Disease state Indication licensed products 11 PID or PHID Rx of PID states or for increase of Ab levels in PID or for replacement therapy of PID states in which severe impairment of Ab-forming capacity 5 ITP rapid increase in plt.count is needed to prevent bleeding, control bleeding, or both in ITP or to allow patient with ITP to undergo surgery 3 Kawasaki prevention of coronary artery aneurysms 2 B-cell CLL prevention of bacterial infections in patients with hypogammaglobulinemia, recurrent bacterial infections, or both associated with B-cell CLL 1 HIV infection Pediatric HIV to decrease frequency of serious and minor bacterial infections and frequency of hospitalization and increase time free of serious bacterial infection 1 BM BM transplant recipients ≥ 20 years of age to decrease transplantation risk of septicemia and other infections, interstitial pneumonia of infectious or idiopathic causes, and acute GVHD in first 100 days after transplantation J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 21.  Primary antibody deficiency disorder  Acute phase of Kawasaki disease  ITP AIHA  GBS MG  Pemphigus, Toxic epidermal necrolysis  Hemaphagocytic lymphohistiocytosis (HLH)
  • 22.  Categorization of evidence and basis of recommendation  Ia From meta-analysis of randomized controlled studies  Ib From at least 1 randomized controlled study  IIa From at least 1 controlled trial without randomization  IIb From at least 1 other type of quasiexperimental study  III From nonexperimental descriptive studies, eg.comparative, correlation, or case-control studies  IV From expert committee reports or opinions or clinical experience of respected authorities or both  Strength of recommendation  A Based on category I evidence  B Based on category II evidence or extrapolated from category I evidence  C Based on category III evidence or extrapolated from category I or II evidence  D Based on category IV evidence or extrapolated from category I, II, or III evidence J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 23. Benefit Disease Evidence Strength of category recommendation Definitely PID with absent B cells IIb B beneficial Primary immune defects with IIb B hypogammaglobulinemia and impaired Specific Ab production Probably CLL with reduced IgG and history of Ib A beneficial infections Prevention of bacterial infection in HIV- Ib A infected children PID with normogammaglobulinemia and III C impaired specific Ab production J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 24. Benefit Disease Evidence Strength of Benefit Disease category Evidence recommendation Strength of category recommendation Definitely Graves ophthalmopathy Ib A Definitely beneficial PID with absent B cells IIb B beneficial Idiopathic thrombocytopenic purpura Ia A Primary immune defects with IIb B hypogammaglobulinemia and impaired Probably Specific Ab production Dermatomyositis and polymyositis IIa B Probably beneficial CLL with reduced IgG and history of Ib A beneficial infections Autoimmune uveitis IIa B Prevention of bacterial infection in HIV- Ib A infected children J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 25.  50 children with acute ITP  26 observed with no therapy,12 IVIG, 12 MDMP  % of patients whose platelet > 20 and > 50 x 109/L at 3 days after starting therapy significantly higher in both IVIG and MDMP groups than in no therapy group (p < .01),  no significant difference at 10 and 30 days after initiation between 3 groups (p > .05 in each comparison)  suggest :  therapy not increase rate of recovery  but shortens duration of thrombocytopenia in the first days  If extensive bleeding and decision is to treat, both IVIG and MDMP are equally effective Pediatr Hematol Oncol 2002;19:219-25
  • 26.  METHODS: In a 2:1-randomized study 23 children  dexa (0.6 mg/kg /d for 4 days once monthly for 6 months, n = 15)  IVIg (800 mg/kg iv once monthly for 6 months, n = 8)  After 4 courses of treatment crossover offered to nonresponders  total of 20 children received dexamethasone and 11 received IVIg  RESULTS:  1/ 8 IVIg and 2 / 15 dexamethasone CR  2 / 15 dexamethasone partial response  1/8 IVIg and 5 /15 dexamethasone discontinued treatment  5 patients crossed over from IVIg to dexamethasone ( 1 CR)  3 from dexamethasone to IVIg (none responded).  5/ 20 dexamethasone complete or partial response  1 / 11 IVIg patients CR  Platelet 30,000 by day 3 were reached in 9 /12 (75%) dexamethasone and all 8 IVIg  CONCLUSIONS: Treatment with pulsed high-dose dexamethasone is not always effective in children with chronic ITP, but it is worth trying in severe symptomatic chronic childhood ITP J Pediatr Hematol Oncol 2003;25: -
  • 27.  compared IVIg with high-dose MP in adults with severe AITP  assessed efficacy of subsequent oral steroids compared with placebo  Primary outcome : number of days with platelet 50,000 within first 21 days  METHODS:  122 severe AITP (platelet count < or =20,000)  randomisation A : receive either IVIg or high-dose MP on days 1-3 then  randomisation B : receive either oral prednisone or placebo on days 4-21  FINDINGS:  number of days : 18 in IVIg ,14 in high-dose MP (p=0.02)  Percentage of patients ,platelet 50,000 on days 2 and 5  7% and 79%, respectively, in IVIg  2% and 60%, respectively, in high-dose MP (p=0.04)  Prednisone more effective than placebo for all short-term endpoints  IVIg & prednisone platelet 50,000 for 18.5 days , high-dose MP and prednisone for 17.5 days (p=0.005)  INTERPRETATION: IVIg and oral prednisone seems more effective than high-dose MP and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated Lancet 2002;359:23-9
  • 28. Benefit Disease Evidence Strength of category recommendation Definitely Definitely PID with absent B cells GBS ,CIDP IIb Ia B A beneficial beneficial Primary immune defects with IIb B MMN Ia A hypogammaglobulinemia and impaired Probably LEMS Specific Ab production Ib A beneficial Probably CLL with reduced IgG and history of Ib A beneficial infections MG Ib-IIa B Prevention of bacterial infection in HIV- -IgM antimyelin-associated glycoprotein Ib Ib A A infected children paraprotein–associated peripheral neuropathy -Stiff-man syndrome PID with normogammaglobulinemia and III C impaired specific Ab production J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 29.  multicenter trial  METHODS: GBS < 2 weeks and unable to walk independently  assigned to receive 5 PE or 5 doses of ivig (0.4 g/ kg/day)  outcome : improvement at 4 weeks of motor function  RESULTS:  150 patients treated  strength had improved in 34 % treated with PE, 53% treated with ivig (difference, 19 %; 3-34%; P = 0.024).  median time to improvement = 41 days with PE and 27 days with IVIg (P = 0.05)  IVIg group significantly fewer complications and less need for artificial ventilation.  CONCLUSIONS: In acute GBS, treatment with ivig at least as effective as plasma exchange and may be superior. N Engl J Med 1992;326:1123-9.
  • 30.  international, multicentre, randomised trial  383 adult with GBS  METHODS: 5PE (8-13 days), IVIg (0.4 g/kg/d for 5 days), or PE course immediately followed by IVIg course  inclusion criteria : severe disease and onset within 14 days. Patients were F/U for 48 weeks.  FINDINGS:  mean improvement 0.9 (SD 1.3) in 121 PE-group patients, 0.8 (1.3) in the 130 IVIg-group patients, and 1.1 (1.4) in 128 patients received both treatments  no significant difference between any of treatment groups in secondary outcome measures  INTERPRETATION: In treatment of severe GBS during first 2 weeks after onset of neuropathic symptoms, PE and IVIg had equivalent efficacy. The combination of PE with IVIg did not confer a significant advantage. Lancet 1997;
  • 31.  RDBPC trial of IVIG treatment in MG  Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo  Primary measurement : change in quantitative MG Score (QMG) at day 42  15 patients (6 to IVIG; 9 to placebo)  At day 42, no significant difference in primary or secondary outcome measurements between 2 groups.  In subsequent 6-week open-label study of IVIG, positive trends were observed. Muscle Nerve 2002;26:549-52.
  • 32.  87 MG exacerbation  3 PE (n = 41), or IVIg (n = 46) 0.4 gm/kg /d further allocated to 3 (n = 23) or 5 days (n = 23)  main end point : myasthenic muscular score (MSS) between randomization and day 15  MSS similar in both groups (median value, +18 in PE group and +15.5 in IVIg group, p = 0.65)  Similar efficacy, although slightly reduced in the 5- day group was observed with both i.v.Ig schedules  tolerance of IVIg better than PE , 8 in PE group and 1 in IVIg group (p = 0.01)  IVIg is alternative for treatment of MG crisis. small sample sizes in our trial, however, could explain why difference in efficacy was not observed Ann Neurol
  • 33.  12 patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months  evaluated clinically using quantified MG clinical score (QMGS) before and at F/U visits after each treatment  1 week after treatments, patients received PE showed significant improvement in QMGS compared to baseline but some improvement after IVIG ,not reach statistical significance  4 weeks after both PE and IVIG ,significant improvement in QMGS compared to baseline  1 and 4 weeks after treatment, no significant difference between 2 treatments was found  Both treatments have clinically significant effect 4 weeks out in chronic MG, but improvement more rapid onset after PE than IVIG. Artif Organs, Vol. 25, No. 12, 2001
  • 34.  retrospective multicenter chart review  Compare efficacy and tolerance of (28/27)PE and (26/24)IVIg in treatment of 54 episodes of myasthenic crisis  PE (compared with IVIg) was associated with superior ventilatory status at 2 weeks (partial F = 6.2, p = 0.02) and 1 month functional outcome (partial F = 4.5, p = 0.04)  However, complication rate higher with PE compared with IVIg (13 vs 5 episodes, p = 0.07).  IVIg : BUN elevation (2),infections(2),CV instability (1)  PE : Infections (6), CV instability (6), coagulopathy (1) Neurology 1999;52:629-32
  • 35. Benefit Disease Evidence Strength of category recommendation Definitely Kawasaki disease PID with absent B cells Ia IIb A B beneficial CMV-induced pneumonitis in Primary immune defects withsolid organ Ib IIb A B transplants hypogammaglobulinemia and impaired Specific Ab production Probably Neonatal sepsis Ia A Probably beneficial CLL with reduced IgG and history of Ib A beneficial infections -Rotaviral enterocolitis Ib A Preventioninfections in lymphoproliferative -Bacterial of bacterial infection in HIV- Ib A infected children diseases -Staphylococcal toxic shock III C PID with normogammaglobulinemia and -Enteroviral meningoencephalitis III C impaired specific Ab production J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 36.  Study design:  case-control study  KD (n = 178; 89 matched pairs) diagnosed 1987 - 1999  89 received IVIG at day 5 or earlier matched to patients diagnosed within 4 weeks and given IVIG at days 6 to 9 of fever  Results:  Patients treated on day 5 or less of fever shorter total fever duration (5.2 days vs 8.0 days, P < .0001), longer fever after IVIG treatment (1.5 ± 1.9 days vs 0.8 ± 1.3 days, P = .008), and less coronary artery ectasia at 1 year after KD onset (4% vs 16%, P = .02).  Patients treated on day 5 or less of fever had higher levels of serum albumin and ALT , lower platelet count than control during acute phase.  Conclusions: Early treatment of KD resulted in less coronary ectasia at 1 year after KD onset but not associated with quicker resolution of fever, increased number of treatment failures, increased need for adjunctive therapy, LOS, development of coronary artery lesions.  IVIG on or before 5 days of fever resulted in better coronary outcomes and decreased total length of time of clinical symptoms. J Pediatr 2002;140:450-5
  • 37.  METHODS :  multicenter, randomized, controlled trial  549 acute KD receive gamma globulin ( single infusion 2 g /kg over 10 hours or daily infusions of 400 mg /kg for 4 days  Both groups received aspirin (100 mg/kg/d through 14th day , then 3 to 5 mg /kg/d)  RESULTS:  Relative prevalence of coronary abnormalities, with 4-day regimen, as compared with single-infusion regimen  1.94 (1.01 - 3.71) 2 weeks after enrollment  1.84 ( 0.89 - 3.82) 7 weeks after enrollment  single-infusion regimen lower mean temp. while hospitalized (day 2, P <0.001; day 3, P = 0.004), shorter mean duration of fever (P = 0.028). inflammation marker moved more rapidly toward normal. Lower IgG levels on day 4 associated with higher prevalence of coronary lesions (P = 0.005) and with greater degree of systemic inflammation  2 groups similar incidence of AEs (including new or worsening CHF in 9 children), occurred in 2.7 % of children overall. All AEs were transient.  CONCLUSIONS. In acute KD, single large dose of IVIg more effective than conventional regimen of 4 smaller daily doses and is equally safe. . N Engl J Med 1991;324:1633-9
  • 38.  METHODS. All published studies in all languages from 1967 – 1993  children in studies received: (1) ASA alone, (2) low IVIG (< or = 1 g/kg) and ASA, (3) high IVIG (> 1 g/kg) and ASA, (4) single IVIG (> 1 g/kg) and ASA, (5) high IVIG and low ASA (< or = 80 mg/kg), or (6) high IVIG and high ASA (> 80 mg/kg)  RESULTS  proportion of CAA at 30 and 60 days were:  ASA group, 30 days, 22.8% ; 60 days, 17.1%  low-IVIG group, 30 days, 17.3% ; 60 days, 11.1%  high-IVIG group, 30 days, 10.3% ; 60 days, 4.4%  single-IVIG group, 30 days, 2.3% ; 60 days, 2.4%  high-IVIG-low-ASA group, 30 days, 13% ; 60 days, 4.8%  high-IVIG-high-ASA group, 30 days, 9.1% ; 60 days, 4%  CONCLUSION: incidence of CAA both at 30 and 60 days  significantly lower in low-IVIG than in ASA  Lower in high-IVIG than in low-IVIG groups  lower in single-IVIG than in high-IVIG group, but this was noted at 30 days and not at 60 days  no statistically significant difference in incidence of CAA both at 30 and 60 days between high-IVIG-low-ASA and high-IVIG-high-ASA groups. Pediatrics 1995;96: -
  • 39.  OBJECTIVES: evaluate effectiveness of IVIG in treating, and preventing cardiac consequences, of KD in children.  SEARCH STRATEGY: Electronic searches (last searched April 2003)  SELECTION CRITERIA: RCT of IVIg to treat KD were eligible for inclusion.  DATA COLLECTION AND ANALYSIS:  16 trial met all inclusion criteria  MAIN RESULTS:  meta-analysis of IVIG versus placebo  show significant decrease in new CAAs in favour of IVIG, at 30 days RR = 0.74 (0.61 - 0.90) No statistically significant difference was found thereafter  subgroup analysis  significant reduction of new CAAs in children receiving IVIG RR = 0.67 (0.46 - 1.00)  trend towards benefit from IVIG at 60 days (p=0.06)  meta-analysis of 400 mg/kg/day for 5 days vs 2 g/kg in single dose  statistically significant reduction in CAAs at 30 days RR (95%) = 4.47 (1.55 to 12.86)  significant reduction in duration of fever with higher dose  no statistically significant difference between different preparations of IVIG & adverse effects in any group.  CONCLUSIONS: KD should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms Cochrane Database Syst Rev 2003
  • 40. indication Evidence recommendation category Probably TEN IIa B beneficial Might provide Autoimmune III C benefit blistering disease Severe Vasculitides III D and ANCA Severe form of SLE III D J ALLERGY CLIN IMMUNOL APRIL 2006
  • 41. ( Ib ,A ) (IIIb ,C) (III-IV,C-D) ANCA (Ia,B) LN ( III) Eur J Dermatol 2009 ; 19 (1) : 90-98
  • 42. Acta Derm Venereol 2007; 87: 206–218
  • 43. Benefit Disease Evidence Strength of category recommendation Definitely PID with absent B cells IIb B Definitely beneficial Sc therapy can reduce occurrence of IIa B beneficial systemic AEs in selected patients Primary immune defects with IIb B hypogammaglobulinemia and impaired Specific Ab production Maintenance of IgG trough levels >500 in IIb B hypogammaglobulinemic Probably CLL with reduces infectious consequences patients reduced IgG and history of Ib A beneficial infections Expert monitoring of patients receiving IV D IGIV infusions to facilitate management of AEs J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 44. Benefit Disease Evidence Strength of category recommendation Benefit Disease Evidence Strength of category recommendation Probably Providing home-based IGIV therapy for low IIa B beneficial risk patients for AEs can improve patient Definitely QOLwith absent B cells PID IIb B beneficial Use of low IgA content IGIV product for III C IgA-deficient pts having IgG–anti-IgA Ab Primary immune defects with IIb B hypogammaglobulinemia and impaired -Product changes might improve AE IV D Specific Ab production profiles -Premedication can improve mild AEs Probably CLL with reduced IgGIGIV products to -Matching particular and history of Ib A beneficial infections specific patient characteristics to reduce AEs -Stopping infusion or slowing infusion rate to facilitate management of AEs J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 45.  Starting dose : 400–600 mg/kg every 4 weeks  trough level > 500 mg/dl or serum IgG level 300 mg/dl over baseline  Higher trough levels (> 800 mg/dl) may be necessary to prevent chronic pulmonary changes and enteroviral meningoencephalitis  Depend on IgG catabolism and/or control over infections, may have to decrease infusion interval to every 2–3 weeks  may take ≥3 months to achieve steady state after change in dose  Monitor serum BUN, Cr, and LFT every 6–12 months  Keep log of dose, manufacturer, lot number, and reactions for each infusion  For patients with rate-related adverse SEs consider pretreatment with:  Acetaminophen  Diphenhydramine  NSAIDs  Corticosteroids  Consider subcutaneous IVIg in patients with frequent adverse reactions Mark Ballow et al, clinical immunology clinical and practice , third edition.
  • 46. J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 47. Product pH after IgA content ( μg/ml ) Stabilizer or Indication§ reconstitution added regulator Carimune NF 6.6 720 Sucrose PI , ITP Carimune NF 6.6 720 Sucrose PI ,ITP Flebogamma 5-6 50 D-sorbitol PI ,ITP Gamimune N 10% 4.25 Traces Glycine PI,ITP,BMT,HIV Gammagard 5% S/D 6.8 2.2 2% Glucose PI,ITP,CLL,KD Gammaraas 4 <70 sorbitol PI,ITP,CLL,KD Gammagard liquid 4.6-5.1 37 Glycine PI Gammar-P 6.8 25 Sucrose PI Gamunex 4-4.5 46 Glycine PI Iveegam EN 6.4-7.2 10 Glucose PI,KD Octagam 5.1 100 Maltose PI Panglobulin NF 6.6 720 Sucrose PI,ITP Polygam S/D 6.8 2.2 Glucose PI,ITP,CLL,KD J ALLERGY CLIN IMMUNOL APRIL 2006.
  • 48. Brand concentration price Flebogamma 2.5g/50 cc 7,123 B 5g/100 cc 14,185 B 10g/200 cc 27,721 B gammaraas 2.5g/50 cc 5,226 B 5g/100 cc 11,831 B
  • 49.  Premedication  sometimes but not always required  Paracetamol and antihistamines can be useful  Rarely may require corticosteroids  Infusion Starship Children’s Health Clinical Guideline
  • 50.  Infused rate 0.01-0.02ml/kg/min for first 30 mins. ( BW 50kg,30-60 cc/hrs.)  If not any discomfort rate may be increased up to 0.04 ml/kg/mins.( BW 50kg,120cc/hrs.)  If tolerated , rate may be higher  If adverse effects occur rate should be reduced or interrupted until symptoms subside  infusion may be resumed at rate which is tolerated by patient
  • 51. Acta Derm Venereol 2007; 87: 206–218
  • 52.  No comparative data among different brands  salt and sugar content, osmolality, total volume infused, rate of infusion, concentration, and total dose of IVIG infused appear to be associated to side-effects  usually transient and selflimited, often arise during first hours of infusion,but can occur up to 72 h following infusion  Rate-related  Chills, Headache, Back pain, Myalgia, Malaise, fatigue, Fever, Pruritus, Rash, Nausea, vomiting, Tachycardia, Chest pain or tightness, Dyspnea, Hypotension/hypertension Acta Derm Venereol 2007; 87: 206–218
  • 53.  possible consequences of low-level aggregation of IgG, immune complex formation and complement activation or, in certain cases, to sugar content of IVIG product  Overcome by reducing rate of infusion, administering corticosteroids, antihistamines, NSAIDs, and/or acetaminophen before beginning infusion Acta Derm Venereol 2007; 87: 206–218
  • 54.  Severe headaches  Aseptic meningitis :  may occur after first 24–72 h of high-dose IVIG treatment, last for up to a week  particularly in migraine  dose-related (rarely seen following replacement doses) Acta Derm Venereol 2007; 87: 206–218
  • 55.  Azotemia  Acute renal failure  proximal tubular dysfunction  reversible in almost all cases  most cases ,transient increase Cr, recover completely within days or weeks after end of IVIG treatment  osmotic pressure caused by stabilizing agent  Risk factors : male , age 65 years, pre-existing renal disease, DM, high BP, hypovolemia, obesity, high infusion rate  Prevention : low IVIG concentrations (5% ), low osmotic load (glycine ), infusion rates should be slow  70- 90% of the renal SE associated with sucrose- containing IVIG Acta Derm Venereol 2007; 87: 206–218
  • 56.  Thrombosis/cerebral infarction  Rare ( incidence 0.6% )  Risk factors : prior Hx of stroke, carotid artery stenosis, chronic HT, high blood viscosity states  Pulmonary embolism,DVT  More rarely  Risk factor :Hx of prior thrombosis, immobilization , hyperviscosity state  Myocardial infarction  risk factor :HT, DM, CAD,Hyperviscosity  Posterior leukoencephalopathy syndrome Acta Derm Venereol 2007; 87: 206–218
  • 57.  especiallyin patients with low IgA levels  current improvement in IVIG quality, the incidence of problems with anti-IgA Ab is less problematic than previously, and their presence does not preclude use of such IVIG preparations Acta Derm Venereol 2007; 87: 206–218
  • 58. Acta Derm Venereol 2007; 87: 206–218
  • 59.  Cardiac rhythm abnormalities  Coagulopathy  Hemolysis – alloantibodies to blood type A/B  Cryoglobulinemia  Neutropenia ( transient ,D4-5 )  Decrease lymphocyte counts, particular CD4  Alopecia  Uveitis  Noninfectious hepatitis Mark Ballow et al, clinical immunology clinical and practice , third edition.
  • 60.  Mode of action of IVIg  Functional blockade of Fc receptors  Auto-Ab neutralization and inhibition of auto-Ab production  Complement inhibition  Modulation of cytokine and cytokine antagonist production  Activation or functional blockade of death receptor Fas (CD95)  Modulation of dendritic cell properties  Increased expression and signalling through inhibitory Fc-receptor, Fc gamma RIIB  Enhancing steroid sensitivity ( enhancement glucocorticoid receptor-binding affinity )
  • 61.  FDA-approved indication for IVIg  primary or secondary hypogammaglobulinaemias  paediatric HIV infection  chronic B-cell lymphocytic leukaemia  bone marrow transplantation  ITP  Kawasaki disease
  • 62.  Administration  before initiating therapy with IVIG  check LFT, renal function,CBC and viral hepatitis screen  measure Ig levels to exclude IgA deficiency, high titres of RF ,and cryoglobulinaemia  On the day of infusion  monitored (BP HR, temp.) before infusion, every 15 min , for first hour of infusion, and every 30 min for rest of infusion  Initial IVIG infusions are usually initiated at slow rate, if tolerated, then increased every 15 min, and then progressively accelerated in absence of SE  After 2–3 successful infusions, initial rates are often accelerated
  • 63.  Dose  Replacement therapy : 400-600 mg/kg  Immunomodulatory indication : 2g/kg  Drug interaction  No drug interaction  Not adminisitered at the same time as attenuated lived vaccines (MMR)