Disclaimer
This information collection is a core HTA, i.e. an extensive analysis of one or more health technologies using all nine domains of the HTA Core Model. The core HTA is intended to be used as an information base for local (e.g. national or regional) HTAs.

Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment

Immunoglobulins (IGG) compared to placebo, not doing anything or Usual supportive care in the treatment of Alzheimer’s disease in elderly AD is diagnosed mostly in people over 65 years of age, although there is an early-onset form that can occur much earlier. According to Wikipedia in 2006, there were 26.6 million sufferers worldwide.

(See detailed scope below)

HTA Core Model Application for Pharmaceuticals (2.0)
Core HTA
Published
Tom Jefferson (Agenas - Italy), Marina Cerbo (Agenas - Italy), Nicola Vicari (Agenas - Italy)
Alessandra Lo Scalzo (Agenas), Anna-Theresa Renner (GOG), Antonio Migliore (Agenas), Ingrid Wilbacher (HVB), Luca Vignatelli (ASSR RER), Luciana Ballini (ASSR RER), Nadine Berndt (CEM), Nicola Vicari (Agenas), Plamen Dimitrov (NCPHA), Susanna Maltoni (ASSR RER), Ricardo Ramos (INFARMED), Tom Jefferson (Agenas)
Agenas - Agenzia nazionale per i servizi sanitari regionali
AAZ (Croatia), ASSR RER (Italy), Avalia-t (Spain), CEM (Luxembourg), GÖG (Austria), HAS (France), HVB (Austria), IER (Slovenia), INFARMED (Portugal), ISC III (Spain), NCPHA (Bulgaria), NIPH (Slovenia), NSPH (Greece), NSPH MD (Romania), SBU (Sweden), SNHTA (Switzerland), THL (Finland), UTA (Estonia).
13.1.2014 12.32.00
30.11.2015 11.18.00
Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 20 September 2021]. Available from: http://corehta.info/ViewCover.aspx?id=267

Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment

<< Health Problem and Current Use of the TechnologySafety >>

Description and technical characteristics of technology

Authors: Jesús González-Enríquez, Nadine Berndt, Houria Mouas

Summary

Features of the technology

Intravenous immunoglobulins (IVIG), human normal immunoglobulin for intravascular administration (ATC code J06BA02), is a medicinal product derived from human plasma of at least thousands of healthy voluntary donors, prepared industrially, containing polyclonal antibodies to produce passive immunity and other protective effects. Human normal immunoglobulin is a highly purified protein extracted from human plasma. It contains immunoglobulin G (IgG), which is a type of antibody. IgG works by restoring abnormally low IgG levels to their normal range in the blood.

There are several IVIG producers and many market authorized presentations of the product. The resulting products are generally believed to be equally effective for treatment of the autoimmune and immunodeficiency disorders. Products presentations vary in concentration of human normal immunoglobulins in 1 ml of solution.

There has been a rapid expansion in the use of intravenous immunoglobulin (IVIG) for an ever growing number of conditions and often used more extensively than the authorized indications (“off-label use”). IVIG has had a major impact in neurology, haematology, immunology, rheumatology and dermatology. Intravenous immunoglobulin (IVIG) has been successfully used to treat a number of immune-mediated diseases of the central and peripheral nervous system. Although underlying mechanisms of action of IVIG have not been fully explained, it is known that IVIG can interfere with the immune system at several levels. IVIG is being used as a treatment in many different conditions, including primary and secondary antibody deficiency states, haematological diseases, neurological diseases and other conditions.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV, and for the non-enveloped viruses HAV and parvovirus B19.

There is reassuring clinical experience regarding the lack of hepatitis A or Parvovirus.

B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.

It is strongly recommended that every time that IVIG preparation is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

Serious reactions are uncommon. Adverse reactions occur more often when a patient is either receiving IVIG for the first time, or switching from one preparation to another or when there has been a long interval since the previous infusion. Certain patient groups are at higher risk for serious complications, such as those receiving high dose IVIG, patients with dehydration, the elderly, and those with preexisting renal or cardiovascular disorders, previous IVIG treatment complications, history of migraine, diabetes, concomitant use of nephrotoxic drugs, sepsis and fluid volume depletion. Many reactions are dose rate-related. Hematologic and thrombotic complications include hemolysis, neutropenia, and thrombotic and thromboembolic events. Some risk factors, such as high doses of IVIG, and certain underlying disorders, have been identified. The most important renal complication is acute renal failure, which is caused by sucrose-containing preparations, but can occur with any IVIG product.

Intravenous immunoglobulin (IVIG) products are being investigated as potential agents for treatment or prevention of AD. Polyclonal naturally occurring autoantibodies against amyloid β are found in serum of healthy persons and are reduced in AD patients.

IVIG has not been approved for prevention or treatment of AD and mild cognitive impairment. IVIG products are thought to contain the full range of antibodies present in the human repertoire. IVIG’s mechanisms of action in different disorders are generally poorly understood. It contains several antibodies that have the potential to reduce AD-type pathology, but whether these antibodies can actually do so is unclear. The IVIG trials reported to date in AD patients have produced conflicting findings. Newer research and developing human trials are becoming established for the use of intravenous immunoglobulins (IVIG) for the treatment and prevention of Alzheimer’s disease. At present there is no cure for AD. Symptomatic treatment of dementia with cholinesterase-inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists is considered as standard of care, particularly in mild to moderate Alzheimer’s disease. In addition to the symptomatic treatments currently marketed, a host of potentially disease-modifying therapies have been studied, and numerous others are in development. At present time there is no effective drug to treat or delay the progression from mild cognitive impairment (MCI) to dementia.

Investments and tools required to use the technology

IVIG is usually administered in an infusion center or health care facility, indicated by specialized medical staff and supervised by health professionals. IVIG can be given in the hospital, doctor’s office, or patients’ home. In any setting, nurses administer most of the transfusions. They should complete an accredited blood transfusion education program and be assessed upon their competency. Accredited nurses are responsible for checking blood and blood products, administering IVIG, monitoring patients during transfusion, and carrying out the appropriate actions should an adverse effect occur, ensuring adequate documentation in the medical notes, and reporting of transfusion reactions or other incidences related to the transfusion.

Detailed documentation of IVIG infusions should include the patient’s current health status and any changes in this status in the period between IVIG infusions; serological testing; record of brand, manufacturer, lot number, expiry date, dose and identification of the patient, any pre-medications which were given; time duration the infusion and specific rate titrations which were made; and any problems or adverse reactions the patient experienced during the infusion and how they were managed. A signed informed and written consent should be obtained from the patient, who should have received full information on the description of IVIG, their nature of blood product, the associated risks and benefits as well as alternatives to this treatment. The administration of IVIG should be carefully monitored and observed for any symptoms or alteration of vital signs throughout the infusion period and after administration. In addition, a monitoring of the renal function and diuresis is required as well as a good hydration of the patient.

Quality controls are required to guarantee the consistency of IVIG batches and to limit the risks of adverse reactions that have shown to be linked to the presence of certain proteins, biological ⁄microbial or chemical impurities. A set of quality control assays are needed to guide manufacturers in the development of IVIG preparations, to control the conditions of production and to guarantee the quality, safety and consistency of the products. Prescribed manufacturing procedures at the plasma collection centers and plasma-testing laboratories need to be designed in that way that they reduce the risk of transmitting viral infection. Risk reducing measures include careful selection of donors for plasma pools, testing for viral markers at multiple stages which allow for the detection of plasma viruses and the application of rigorously validated methods of testing. Quality controls for plasma derivatives include determination of chemical parameters, protein content, content of stabilizers and residues of chemicals used for the production or viral inactivation and various safety parameters. Some IVIGs products require refrigeration whereas others can be stored at room temperature. As such, lyophilized products are generally stored at room temperature before reconstitution. However, all liquid IVIG products optimally require refrigerated transport and storage between 2°C and 8°C. Blood products should be transported in dedicated and validated containers and be stored within glass containers, which are closed with rubber stoppers. It is important to follow the manufacturer’s specifications regarding storage and refrigeration requirements of each product, since the recommendations may vary per IVIG product.

Training and information needed for utilizing the technology

The health professional using IVIG requires specific knowledge and skills in order to be competent to treat patients with IVIGs. A hospital based IVIG program should provide education, training and protocols for staff to ensure the appropriate management and use of IVIGs, including transport, storage, use of equipment and infusion techniques. The training should include education related to documentation, patient consent, difference among IVIG brands, selection of a brand on the basis of patients’ risk factors, contraindications, needs, action plans for adverse events, rapid infusion protocols, and setup of infusion pumps, tubing and filter equipment.

Patients should be eligible for IVIGs only in case they give consent for transfusion of blood and/or blood products. One or several patient and/or family education sessions may be required to inform patients and/or family about what IVIG are and what they are used for, the fact that IVIGs are not licensed for use in the treatment of Alzheimers’ disease and mild-cognitive-impairment (off-label use), what one needs to know before using IVIGs, how and how often it is administered, the approximate duration of each infusion times, potential risks and benefits of its use, the potential of virus transmissions, contra-indications, so that informed consent may be obtained. Information about such things as new modalities of treatment, legislative initiatives and insurance issues may also be valuable. Patients and their families should equally be provided with written information brochures concerning the IVIGs. A risk assessment may be carried out to ensure the patient and family understand the need for treatment and how it is administered. 

Introduction

Intravenous immunoglobulins (IVIG), human normal immunoglobulin for intravascular administration (ATC code J06BA02), is a medicinal product derived from the pool of human plasma of at least thousands of healthy voluntary donors, prepared industrially, containing polyclonal antibodies to induce passive immunity and other protective effects. Human normal immunoglobulin is a highly purified protein extracted from human plasma. It contains immunoglobulin G (IgG), which is a type of antibody. IgG acts by restoring abnormally low IgG levels to their normal range in the blood.

There are several IVIG producers and many market authorized presentations of the product. The resulting products are generally believed to be equally effective for treatment of the autoimmune and immunodeficiency disorders. Products presentations vary in concentrations of human normal immunoglobulins in 1 ml of solution.

There has been a rapid expansion in the use of intravenous immunoglobulin (IVIG) for an ever growing number of conditions. IVIG has had a major impact in neurology, haematology, immunology, rheumatology and dermatology.

Intravenous immunoglobulin (IVIG) has been successfully used to treat a number of immune-mediated diseases of the central and peripheral nervous system. Although underlying mechanisms of action of IVIG have not been fully explained, it is presumed that IVIG can interfere with the immune system at several levels. IVIG has not been approved for prevention or treatment of AD and mild cognitive impairment. IVIG products contain the full range of antibodies present in normal population. IVIG’s mechanisms of action in different disorders are generally poorly understood. It contains several antibodies that have the potential to reduce AD-type pathology, but whether these antibodies can actually do so is unclear. Newer research and human clinical trials are conducted for the use of intravenous immunoglobulins (IVIG) for the treatment and prevention of Alzheimer’s disease.

The aim of this Domain is to describe and review the technical characteristics of IVIG. The aspects considered in this domain are correlated with the selected relevant issues and research questions. We try to describe the technology and its technical characteristics to get an overall understanding on its functioning, indications and use.

Methodology

Frame

The collection scope is used in this domain.

TechnologyImmunoglobulins (IGG)
Description

Naturally occurring proteins produced by the body’s immune system to combat foreign antigens

Intended use of the technologyTreatment

Treatment of Alzheimer’s disease

Target condition
Alzheimer’s disease
Target condition description

Alzheimer's disease (AD) or Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death.

Target population

Target population sex: Any. Target population age: elderly. Target population group: Patients who have the target condition.

Target population description

AD is diagnosed mostly in people over 65 years of age, although there is an early-onset form that can occur much earlier. According to Wikipedia in 2006, there were 26.6 million sufferers worldwide. 

Comparisonplacebo, not doing anything or Usual supportive care
Description

There is no MA for IGGs for AD yet and there is no other intervention licensed for use in AD so the comparison would have to be against placebo or best supportive care

Outcomes
  • Description of aims of technology (TECH)
  • Regulatory status (CUR)
  • Cognitive function (EFF)
  • Harms (SAF)
  • Cost effectiveness compared to alternatives (ECO)
  • Potential impact on plasma derivative market (ORG/Medico-legal)
  • Impact on family and carers (SOC)
  • Appropriateness of use in relation to solidity of evidence(ETH)

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
B0001Features of the technologyWhat is this technology and the comparator(s)?yesWhat are Intravenous Inmunoglobulins (IVIG)?
What are the potential comparators for IVIG use in Alzheimer’s disease and Mild Cognitive Impairment?
B0002Features of the technologyWhat is the approved indication and claimed benefit of the technology and the comparator(s)?yesWhat is the approved indication and claimed benefit of IVIG?
B0003Features of the technologyWhat is the phase of development and implementation of the technology and the comparator(s)?yesWhat is the phase of development and implementation of intravenous immunoglobulins (IVIG)?
B0004Features of the technologyWho performs or administers the technology and the comparator(s)?yesWho performs or administers IVIG?
B0005Features of the technologyIn what context and level of care are the technology and the comparator used?yesIn what context and level of care are IVIG used?
A0022OtherWho manufactures the technology?yesWho manufactures IVIG?
B0007Investments and tools required to use the technologyWhat material investments are needed to use the technology?yesWhat material investments are needed to use IVIG?
B0008Investments and tools required to use the technologyWhat kind of special premises are needed to use the technology and the comparator(s)?yesWhat kind of special premises are needed to use IVIG?
B0009Investments and tools required to use the technologyWhat equipment and supplies are needed to use the technology and the comparator?yesWhat equipment and supplies are needed to use IVIG?
B0010Investments and tools required to use the technologyWhat kind of data and records are needed to monitor the use of the technology and the comparator?yesWhat kind of data and records are needed to monitor the use of IVIG ?
B0011Investments and tools required to use the technologyWhat kind of registers are needed to monitor the use the technology and comparator?yesWhat kind of registers are needed to monitor the use IVIG?
B0012Training and information needed to use the technologyWhat kind of qualification and quality assurance processes are needed for the use or maintenance of the technology?yesWhat kind of qualification and quality assurance processes are needed for the use or maintenance of IVIG?
B0013Training and information needed to use the technologyWhat kind of training and information is needed for the personnel/carer using this technology?yesWhat kind of training and information is needed for the personnel/carer using IVIG?
B0014Training and information needed to use the technologyWhat kind of training and information should be provided for the patient who uses the technology, or for his family?yesWhat kind of training and information should be provided for the patients who uses IVIG o for their families?
B0015Training and information needed to use the technologyWhat information of the technology should be provided for patients outside the target group and the general public?noPotential intervention for a specific clinical situation. In the current situation it is not relevant to examine the needs of information provision for the general population or patients outside the target group, because the intervention is highly specific. However, if the intervention will turn out to be effective in the future, there might be an interest to provide information on the IVIGs to the relevant target population and probably also to the general public, thus they are informed about the existence of this treatment.

Methodology description

Domain frame

The project scope is applied in this domain.

Information sources

- Basic systematic search. Common (basic) literature search strategy run for the whole project (Immuno database).

- Additional search for published literature in PubMed and internet search of grey literature using Google, HTA database.  Review of the reference lists and bibliographies of selected studies identified through the basic systematic search.

- Manufacturers and companies web sites, Micromedex Drugdex Database.

- Search for IVIG authorization of immunoglobulins in EU website, EMEA data files, national and European law, other European notified bodies.

Quality assessment tools or criteria

No quality assessment tool was used. We use unsystematic approach and selection of relevant updated general reviews and specific documents.

Analysis and synthesis

The sources were sufficient to answer the questions. We did not perform additional data analysis. No quality assessment of the sources was made.

The results are presented in text format, supplemented by overview tables.

Descriptive analysis on different information sources. The assessment elements questions are answered and reviewed by cooperation of Domain investigators.

Result cards

Features of the technology

Result card for TEC1a: "What are Intravenous Inmunoglobulins (IVIG)?" and TEC1b: "What are the potential comparators for IVIG use in Alzheimer’s disease and Mild Cognitive Impairment?"

View full card
TEC1a: What are Intravenous Inmunoglobulins (IVIG)?
Method
Result

Importance: Important

Transferability: Completely

TEC1b: What are the potential comparators for IVIG use in Alzheimer’s disease and Mild Cognitive Impairment?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC2: "What is the approved indication and claimed benefit of IVIG?"

View full card
TEC2: What is the approved indication and claimed benefit of IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for CUR17 / TEC3: "What is the phase of development and implementation of intravenous immunoglobulins (IVIG)?"

View full card
CUR17 / TEC3: What is the phase of development and implementation of intravenous immunoglobulins (IVIG)?
Result

Importance: Critical

Transferability: Completely

Result card for TEC4: "Who performs or administers IVIG?"

View full card
TEC4: Who performs or administers IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC5: "In what context and level of care are IVIG used?"

View full card
TEC5: In what context and level of care are IVIG used?
Method
Result

Importance: Optional

Transferability: Partially

Other

Result card for TEC6: "Who manufactures IVIG?"

View full card
TEC6: Who manufactures IVIG?
Method
Result

Importance: Important

Transferability: Partially

Investments and tools required to use the technology

Result card for TEC7: "What material investments are needed to use IVIG?"

View full card
TEC7: What material investments are needed to use IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC8: "What kind of special premises are needed to use IVIG?"

View full card
TEC8: What kind of special premises are needed to use IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC9: "What equipment and supplies are needed to use IVIG?"

View full card
TEC9: What equipment and supplies are needed to use IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC10: "What kind of data and records are needed to monitor the use of IVIG ?"

View full card
TEC10: What kind of data and records are needed to monitor the use of IVIG ?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC11: "What kind of registers are needed to monitor the use IVIG?"

View full card
TEC11: What kind of registers are needed to monitor the use IVIG?
Method
Result

Importance: Unspecified

Transferability: Unspecified

Training and information needed to use the technology

Result card for TEC12: "What kind of qualification and quality assurance processes are needed for the use or maintenance of IVIG?"

View full card
TEC12: What kind of qualification and quality assurance processes are needed for the use or maintenance of IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC13: "What kind of training and information is needed for the personnel/carer using IVIG?"

View full card
TEC13: What kind of training and information is needed for the personnel/carer using IVIG?
Method
Result

Importance: Important

Transferability: Partially

Result card for TEC14: "What kind of training and information should be provided for the patients who uses IVIG o for their families?"

View full card
TEC14: What kind of training and information should be provided for the patients who uses IVIG o for their families?
Method
Result

Importance: Important

Transferability: Partially

References

  1. Duff K. You can make a difference in the administration of intravenous immunoglobulin therapy. J Infus Nurs 2006; 29 (3S), S5-S14.
  2. The Consensus Working Group. Present and future uses of IVIG: A Canadian multidisciplinary consensus-building initiative. Can J Allergy Clin Immunol 1997; 2: 176-207.
  3. Laupland, KB. Polyclonal intravenous immunoglobulin for the prophylaxis and treatment of infection in critically ill adults. Can J Infect Dis 2002; 13 (2):100-106.
  4. WHO. Requirements for the collection, processing, and quality control of blood, blood components, and plasma derivatives. WHO technical Report Series 1989, No. 786, Annex 4.
  5. Department of Health. Clinical guidelines for immunoglobulin use: update to second edition. DH, 2011.
  6. Micromedex Drugdex Database, Truven Health Analytics, 2014. (Last Modified: July 03, 2014). Accessed the 3th of July 2014.
  7. Loeffler DA. Intravenous immunoglobulin and Alzheimer’s disease: what now? J Neuroinflamm 2013, 10:70.
  8. EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol 2008, 15: 893–908
  9. Dodel R, Neff F, Noelker C, Pul R, Du Y, Bacher M, Du Y. Intravenous Immunoglobulins as a Treatment for Alzheimer’s Disease: Rationale and Current Evidence. Drugs 2010; 70(5), 513-528.
  10. Moreth J, Mavoungou C, Schindowski K. Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets? Immun Ageing 2013, 10:18
  11. Dodel R, Hampel H, Depboylu C, Lin S, Gao F, Schock S, Jäckel S, Wei X, Buerger K, Höft C, Hemmer B, Möller HJ, Farlow M, Oertel WH, Sommer N, Du Y. Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease. Ann Neurol 2002, 52:253–256.
  12. Dodel R, Du Y, Depboylu C, Hampel H, Frölich L, Haag A, Hemmeter U, Paulsen S, Teipel SJ, Brettschneider S, Spottke A, Nölker C, Möller HJ, Wei X, Farlow M, Sommer N, Oertel WH. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J Neurol Neurosurg Psychiatry 2004, 75:1472–1474.
  13. Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009, 30:1728–1736.
  14. Weksler M, Szabo P, Relkin N. IVIG therapy of mild to moderate Alzheimer’s disease patients showed significant benefits as measured by neuroimaging and neuropsychological testing in a phase II, randomized, double blind placebo controlled clinical study. Gerontologist 2010; 50: 449–50.
  15. Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Förster S, Winter Y, Bach JP, Popp J, Alferink J, Wiltfang J, Buerger K, Otto M, Antuono P, Jacoby M, Richter R, Stevens J, Melamed I, Goldstein J, Haag S, Wietek S, Farlow M, Jessen F. Intravenous immunoglobulin for treatment of mild to- moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol 2013, 12:233–243.
  16. Upadhyaya P, Seth V, Ahmad M. Therapy of Alzheimer’s disease: an update, African Journal of Pharmacy and Pharmacology 2010; 4(6), 408-421.
  17. Green Park Collaborative (GPC). Evidence guide document. Design of Clinical Studies of Pharmacologic Therapies for Alzheimer’s Disease. April 2013.
  18. Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological strategies for treatment of Alzheimer´s disease: focus on disease modifying drugs. Br J Clin Pharmacol 2011; 73, 4: 504-517.
  19. Nygaard HB. Current and Emerging Therapies for Alzheimer’s Disease. Clin Ther 2013; 35(19), 1480-1489.
  20. Hort J, O`Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, Sorbi S and Scheltens P on behalf of the EFNS Scientist Panel on Dementia. EFNS guidelines for the diagnosis and management of Alzheimer`s disease. Eur J Neurol 2010, 17: 1236–1248 doi: 10.1111.
  21. NICE technology appraisal guidance 217. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review of NICE technology appraisal guidance 111). April 2014.
  22. Lin JS, O’Connor E, Rossom RC, Perdue LA, Eckstrom E. Screening for Cognitive Impairment in Older Adults: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159: 601-612.
  23. Tricco AC, Soobiah Ch, Berliner S, Ho JM, Carmen H, Ashoor HM, et al. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis. CMAJ 2013; DOI:10.1503
  24. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev 2012; 9: Cd009132)
  25. Birks J, Flicker L. Donepezil for mild cognitive impairment. Cochrane Database Syst Rev 2006; (3):Cd006104.
  26. Cooper C, Li R, Lyketsos C and Gill Livingston Gill. Treatment for mild cognitive impairment: systematic review. BJP 2013; 203, 255–264. doi: 10.1192/bjp.bp.113.127811
  27. Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: Intravenous immunoglobulin in the treatment of neuromuscular disorders Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012; 78:1009-1015.
  28. Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P et al. Guidelines on the Use of Intravenous Immune Globulin for Hematologic Conditions. Transfus Med Rev 2007; 21, No 2, Suppl 1 (April): S9-S56
  29. White-Reid K, Scherf R. Giving intravenous immunoglobulin. Modern Medicine, 2008. Accessed the 20th of June 2014 from http://www.modernmedicine.com/modern-medicine/news/giving-intravenous-immunoglobulin
  30. European Medicines Agency. Accessed the 4th of June 2014 from http://www.ema.europa.eu/
  31. Food and Drug Administration. Accessed the 5th of June 2014 from www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm133691.htm
  32. New Zealand Clinical Immunology Group. Nursing guidelines for administration of subcutaneous immunoglobulin (SCIg). 3rd Version. New Zealand: NZCIG. 2013. Accessed the 20th of June 2014 at: http://www.healthpoint.co.nz/
  33. ACT Health. Standard Operating Procedure: Intravenous Immunoglobulin (IVIg) Administration: Canberra, Australia: ACT Health. 2013. Accessed the 20th of June 2014 from http://www.act.gov.au/
  34. Octapharma. Immune Globulin Intravenous (Human) 5% Solvent/Detergent Treated. 2007. Accessed the 25th of June 2014 at: http://www.abopharmaceuticals.com/ProductSheets/Octagam_PI.pdf
  35. Octapharma. Package leaflet: information for the user - Octagam 10% solution for infusion. 2014. Accessed the 18th of June 2014 at: http:// www.medicines.org.uk
  36. Baxter Healthcare Corporation. Kiovig (Normal Immunoglobulin): Product Information. 2011.  Accessed the 18th of June 2014 at: http://www.baxterhealthcare.com.au/downloads/healthcare_professionals/cmi_pi/kiovig_pi.pdf
  37. Younger MEM, Buckley RH, Belser CM, Moran K, Duff C, Epland KB, et al. IDF guide for nurses: immunoglobulin therapy for primary immunodeficiency diseases. 3rd edition. Towson, MD: Immune Deficiency Foundation. 2012.
  38. World Health Organization. The International Pharmacopoeia (4th Edition). WHO Department of Essential Medicines and Pharmaceutical Policies (EMP), NGO/WIT and its logistic partner HumanityCD Ltd, and the University of Waikato, New Zealand. 2013. Accessed the 25th of June 2014 from http://apps.who.int/phint/en/p/about/
  39. Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang 2010; 98, 12-28.
  40. Gelfand EW. Critical decisions in selecting an intravenous immunoglobulin product. J Infus Nurs 2005; 28(6), 366-374.
  41. Gelfand EW. Differences between IGIV products: impact on clinical outcome. Int Immunopharmacol 2006; 6, 592-599.
  42. Rosenthal K. Intravenous Immunoglobulin. Resource Nurse. 2007. Accessed the 20th of June 2014 from http://www.resourcenurse.com/feature_ivig.html.
  43. Reid B, Van Allen S., LaGrange CA, Boissoneault N. Protocol recommendations for administration of intravenous immunoglobulin in Canada. J Infus Nurs 2006; 29(3), 158-64.
  44. Malcolmson C, Jones A, Xu-Bayford J. Guideline for immunoglobulin infusions: intravenous and subcutaneous. London, UK: Great Ormond Street Hospital. 2014. Accessed the 20th of June 2014 at: http://www.gosh.nhs.uk/health-professionals/clinical-guidelines/immunoglobulin-infusions-intravenous-and-subcutaneous/
  45. National Blood Authority. Training checklist for home administered subcutaneous immunoglobulin infusion treatment. Lyneham, Australia: National Blood Authority. 2014. Accessed the 18th of June 2014 at: http://www.blood.gov.au/subcutaneous-immunoglobulin
  46. NHS Health Scotland. Clinical guidelines for immunoglobulin use - Second edition update Scotland. Edinburgh: NHS Health Scotland.  2012.Accessed the 20th of June 2014 at: http://www.nsd.scot.nhs.uk/Documents/clinimmumoMarch12.pdf
  47. Chipps E, Skinner C. Intravenous Immunoglobulin: implications for use in the neurological patient. J Neurosci Nurs 1994, 26(1), 8-17.
  48. Gysler, M. Infusion of Intravenous Immune Globulin (IVIG) CPG. The Credit Valley Hospital – Clinical Practice Guidelines. 2012.  Accessed the 18th of June 2014 at: http://www.cvh.on.ca/pro/cpg/Infusion%20of%20Intravenous%20Immune%20Globulin%20__IVIG_%20CPG.pdf
  49. American Academy of Allergy Asthma & Immunology. Guidelines for the site of care for administration of IGIV therapy. Milwaukee, WI: American Academy of Allergy Asthma & Immunology.  2011.Accessed the 20th of June 2014 at https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/Guidelines-for-the-site-of-care-for-administration-of-IGIV-therapy.pdf
<< Health Problem and Current Use of the TechnologySafety >>