Immune Globulin for Patients with Primary Immune Deficiency: An Evidence Based Practice Guideline

Background: The original use of immune globulin (IG) was for replacement in patients with primary immune deficiency (PID). The evidence supporting this stems from the 19650s; however there have not been any rigorously developed evidence based clinical practice guidelines (CPGs) for the use of IG for PID. In 2007, Canadian Blood Services and the National Advisory Committee on Blood and Blood Products in Canada convened a panel of Canadian immunologists and a methodologist to develop a CPG for the use of IG in patients with PID. The objectives of this guideline are

1. to examine the evidence for the use of IG in patients who have PID and

2. to provide guidance for practitioners involved in the care of PID patients and transfusion medicine specialists on the use of IG.

Methods: The panel identified key clinical questions and a systematic, expert and bibliography literature search up to July 2008 was conducted to ensure all relevant publications were included. The panel generated recommendations based on the evidence. The levels of evidence and grading of recommendations were adapted from the Canadian Task Force on Preventative Health Care. To validate conclusions and recommendations, the practice guideline will be sent to immunologists internationally and to a patient representative in September 2008. The guideline will be disseminated to all immunologists, internists and pediatricians in Canada to aid implementation of the guideline. The National Advisory Committee of Blood and Blood Products in Canada will assess the performance of the guideline and will renew the guideline at timely intervals.

Results and Conclusions: The panel identified the following key clinical questions:

1. what is the prevalence of the PIDs that require IG;

2. does treatment with IG improve morbidity and mortality; and

3. what criteria should be used to monitor the effectiveness of IVIG.

The literature search was conducted in August 2007 and updated to July 2008. 1087 citations were reviewed. 101 reports, 1 systematic review and 3 consensus documents/guidelines were included. Current estimates suggest PID is under-diagnosed. Although more than 75% of patients require IG at some point in their treatment, the actual incidence of requiring IG is unknown. There is ample evidence that IG reduces infections, hospitalization and days lost from work/school. There is some evidence to suggest that IG may ameliorate chronic illnesses in patients with PID however, there is no data of the effect of IG on malignancy and insufficient data on the effect of IG on autoimmune disease in this patient population to make a recommendation. Quality of life (QoL) has not been adequately assessed in the literature; however the reduction in infections and hospitalizations likely translates to an improved QoL. Although, there is no evidence to suggest clinical superiority of one IVIG formulation over another, for patients with autoimmune manifestations and PID, there is insufficient evidence that subcutaneous IG is equivalent to IVIG. The vaccination of these patients is an evolving field. Due to the complex nature of the management of patients with PID, the panel recommended assessment by an immunologist prior to the initiation of IG and monitoring by a comprehensive care clinic. Clinical outcomes such as frequency of infections, hospitalization, days missed from school/work should be used to monitor the effectiveness of IVIG. Specific recommendations for dosing and interval of IG therapy were made within the guideline based on the literature The development of a national registry for patients with primary immune deficiency, and the development of a surveillance system for adverse events from IG particularly infections were considered priorities for future development.