J Clin Immunol DOI 10.1007/s10875-014-0057-9
ASTUTE CLINICIAN REPORT
SCIg vs IVIg: Let’s Give Patients the Choice! K. Samaan & M. C. Levasseur & H. Decaluwe & C. St-Cyr & H. Chapdelaine & A. Des Roches & E. Haddad
Received: 6 January 2014 / Accepted: 13 May 2014 # Springer Science+Business Media New York 2014
Introduction Intravenous immunoglobulins (IVIg) and subcutaneous immunoglobulins (SCIg) are equally efficient in preventing serious bacterial infections (1–5) in patients with primary immune deficiency (PID). Currently, SCIg or IVIG use is often based upon physician’s judgment (2, 6). However, in some centers such as ours, patients are given the choice of treatment modality, regardless of the physician’s opinion on “idealness” of the candidate. In this retrospective study of 143 patients with PID treated by immunoglobulin (Ig) replacement, we present our experience regarding patient’s behavior when given choice of hospital-based IVIg versus home-based SCIg.
Methods We retrospectively analyzed our tertiary center pediatric cohort of 143 patients with PID on Ig replacement. All patients, K. Samaan : M. C. Levasseur : H. Decaluwe : C. St-Cyr : A. Des Roches : E. Haddad (*) Department of Pediatrics, University of Montreal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada e-mail: [email protected] H. Chapdelaine Department of Allergy, University of Montreal, Centre Hospitalier Universitaire de Montreal, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada E. Haddad Department of Microbiology and Immunology, University of Montreal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada
regardless of the physician and nurse’s impression of the “idealness” of the candidates, were offered the choice between hospital-based IVIg and home-based SCIg. Patients were separated into 2 cohorts: a “switch” cohort of patients already on IVIg when the choice of route of administration was given to them in 2007 when SCIg became available in Quebec, and a “new” cohort, consisting of patients diagnosed thereafter and thus, given the choice at the beginning of Ig replacement. The physician explained both treatment options in general terms and our clinical nurse provided technical explanations on the methods, along with written information describing the modalities and side effects. In all cases, it was clearly indicated that both routes were equally effective. Importantly, it was emphasized that patients had the choice to change their mind at a later point in time if desired and as many times as desired. IVIg was administered in our day treatment center every 4 weeks. SCIg patients received three weekly 2 h sessions with our clinical nurse, before administering SCIg independently at home. Our institution provided patients with infusion tubing and syringes, and pumps were provided by the Ig company. For patients switching from IVIg to SCIg, SCIg injections consisted of 100 % of their IV dose divided over 4 weeks, and started 1 to 2 weeks after the last IVIg infusion. All starting doses of Ig for new patients were calculated on the basis of 400 mg/kg/4 weeks. IV doses were titrated based upon serum IgG trough levels, avoiding trough levels below 700 mg/dl, while SCIg doses were measured 3 months after the initiation of the treatment and then at every 4 months with the same objective. Patients’ demographics characteristics are shown in Table I.
J Clin Immunol Table I Demographic characteristics of patients in each cohort Switch cohort Switching to SCIg Sex male: n (%) Age at diagnosis in years Age of patients when given choice of treatment in years PID diagnosis: n Common variable immunodeficiency Isolated IgG deficiency IgG class 2 deficiency Combined immunodeficiency Di George syndrome HyperIgE Other
29 (57 %) 7.2 10.7 37 3 3 2 1 0 5*
New cohort Staying on IVIg
11
Starting on SCIg 55 (59 %) 7.1 6.0 39 27 4 3 4 3 12□
Starting on IVIg
8.3
*=1X-linked agammaglobulinemia, 2 X-linked lymphoproliferative disorder, 1 NEMO, 1 Rothman-Thompson syndrome □
=1 X-linked agammaglobulinemia, 3 humoral deficiency not otherwise specified, 3 ataxia-telangiectasia, 1 tricho-hepato-intestinal syndrome, 1 polysaccharide antibody deficiency, 1 ALPS-like syndrome with IgG deficiency, 1 congenital dyskeratosis, 1 hyperIgM PID: primary immunodeficiency
Results
Analysis of Compliance
Analysis of the Patients’ Choice
Poor compliance to SCIg was noted in 3 (6 %) patients in the “switch” cohort and in 7 (9 %) in the “new” cohort. Reasons for non compliance were: monoparental families and poor supervision in pre-teenagers and teenagers, attention-deficit disorder in parents or child, and parental stress regarding the SCIg modality. A switch to IVIg was proposed and these patients eventually decided to switch to IVIg. Two of these patients returned to SCIg treatment 2 and 23 months later without any relapse of poor compliance.
Patients’ choices in both cohorts are shown in Fig. 1. In the “switch” cohort (n=51), all patients but 1 chose to switch to SCIg. After an average follow up of 52 months (range 30– 75 months), 44 patients (88 %) remained on SCIg. In the “new” cohort, almost half of patients (44/92) initially chose SCIg with an additional 35/48 later switching from IVIg to SCIg after an average of 6.8 months. Currently, 74 patients (80 %) in the “new” cohort are on SCIg after an average follow up of 33.2 months (range 7.9–66.3 months). Together, only a total of 13 patients switched from SCIg to IVIg. The reasons noted were change in family situation (parental medical difficulties), pain associated with the frequent injections and compliance issues.
Tolerability SCIg was well tolerated without any systemic reaction. Five patients developed local reactions at injection sites, which resolved by 3 months of treatment. Additionally, 2 of these patients developed hypersensitive subcutaneous nodules at injection sites, which resolved when the sites were rotated. In patients on IVIg, side effects were similar to those seen in the literature (7–9). No cases of anaphylaxis occurred in either cohort. The mean steady-state level of IgG was 920 mg/dl (range 600–1250) for patients under IVIg and 900 mg/dl (range 530–1470) for patients under SCIg (p=0.67).
Analysis of Patient’s Behavior When the Choice was Offered Stress in relation to the need to make a choice was assessed by retrospective analysis of medical and nursing notes. Stress was more obvious in patients from the “new” cohort, since 70 and 30 % of patients exhibited a mild stress in the “new” cohort and in the “switch cohort”, respectively. Despite this stress, patients mentioned that they were reassured by being offered the possibility of changing treatment modality as they wanted.
Discussion We have been able to safely and efficiently give our patients the choice between hospital-based IVIg and home-based SCIg. This attitude of giving the choice without preconceived opinions allowed us to be pleasantly surprised by the perfect
J Clin Immunol
a)
44 stayed on SCIg (88%)
1 patient died of neoplasm
6 switched back to IVIg (12%)
1 returned to SCIg
50 chose to switch to SCIg (98%) 51 patients requiring Ig replacement therapy 1 chose to remain on IVIg (2%)
b)
42 stayed on SCIg (95%) 44 starting on SCIg at onset (48%) 2 switched to IVIg (5%)
92 patients requiring Ig replacement therapy 35 switched to SCIg (73%)
5 switched to IVIg (14%)
2 switched to SCIg
48 starting on IVIg (52%) 13 stayed on IVIg (27%)
Fig. 1 Flowchart of patients’ distribution in two cohorts: a Distribution of patients in the “switch” cohort, who were already on Ig replacement when SCIg became available. b Distribution of patients in the “new” cohort who were offered SCIg therapy at time of diagnosis
compliance observed in 5 of 6 patients, who, if the traditional approach of physician’s selection of patients had been followed, would not have been offered the choice, demonstrating that a medical a priori can be false. Also, providing patients with the opportunity to be responsible for their own health could be a factor that diminishes poor compliance. SCIg became the mainstay of treatment in both cohorts, since among the 142 surviving patients currently, 118 (83 %) are under SCIg, suggesting its association with a better quality of life (QoL). Multiple studies have demonstrated that SCIg is associated with a better QoL (6, 10–13) and this could have contributed to the strong preference we observed for SCIg. However, this study does not allow for such a conclusion for various reasons. Firstly, the location of Ig replacement delivery (home versus hospital) was inherently associated with the route of delivery (SC versus IV). It is possible that if IVIg were administered at home, patients would prefer the IV method to the SC method. Unfortunately, it is not possible in our current medical setup in Quebec to provide home-based IVIg. In addition, one cannot rule out the hypothesis that the setup for IVIg in our center is inconvenient and could contribute to the fact that most of the patients switched from IVIg to SCIg. One would have to conduct a multicenter study, and even doing so would not eliminate the potential problem that in some centers, hospital-administered Ig may be unpleasant.
Secondly, written information provided to patients has not been validated prospectively before the study and one could argue that the presentation of treatment modalities could have been biased and that personal beliefs may have contributed to patients’ decision. However, interestingly, in the “new” cohort, approximately half chose IVIg suggesting that the explanations given to patients regarding choice of modality were likely neutral. Since our center provided patients with free material for SCIg infusion, one could argue that this impacted patients’ choices. A pharmacoeconomic study, previously performed in our center, comparing the costs of IVIg and SCIg, showed that the total cost of SCIg was significantly lower than IVIg from hospital, government, insurance companies and patients perspectives (14). In this pharmacoeconomic study, the costs of tubing, syringes and pumps were applied to the parents’ costs (14), meaning that the cost of materials was offset by the savings in loss of productivity and cost of travel. Therefore, it is likely that even if materials were not provided for free, patients would have chosen SCIg more frequently than IVIg, although it would have probably reduced the percentage of patients choosing SCIg. Altogether, we believe that there is no “ideal candidate” for SCIg or IVIG therapy. In the current medical culture, the patient has become a partner (15, 16), and giving the patient the choice for his/her treatment is very apropos. We demonstrate here that giving patients the choice of Ig replacement is a feasible, safe and efficient strategy.
J Clin Immunol Acknowledgments Elie Haddad is a scholar of Fonds de la Recherche en Santé au Québec (FRQS). Funding Funds to hire a native English speaker to help with editing the final version of the manuscript was provided by CSL Behring. The authors did not work for CSL Behring and CSL Behring was not involved in the design of the study or writing of the manuscript.
References 1. Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M, Subcutaneous Ig GSG. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26(3):265–73. 2. Berger M. Choices in IgG replacement therapy for primary immune deficiency diseases: subcutaneous IgG vs. intravenous IgG and selecting an optimal dose. Curr Opin Allergy Clin Immunol. 2011;11(6):532–8. 3. Chapel HM, Spickett GP, Ericson D, Engl W, Eibls MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20(2):94–100. 4. Ballow M. Immunoglobulin therapy: methods of delivery. The J of allergy and clin immunol. 2008;122(5):1038–9. 5. Haddad E, Barnes D, Kafal A. Home therapy with subcutaneous immunoglobulins for patients with primary immunodeficiency diseases. Transfusion and apheresis science : official j of the World Apher Assoc : official j of the Eur Soc for Haemapheresis. 2012;46(3):315–21. 6. Wasserman RL. Progress in gammaglobulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. J Clin Immunol. 2012;32(6):1153–64. 7. Eibl MM. History of immunoglobulin replacement. Immunol Allergy Clin N Am. 2008;28(4):737–64.
8. Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29(3):173–84. 9. Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the primary immunodeficiency committee of the american academy of allergy, asthma and immunology. The J of allergy and clin immunol. 2006;117(4 Suppl):S525– 53. 10. Kobrynski L. Subcutaneous immunoglobulin therapy: a new option for patients with primary immunodeficiency diseases. Biologics : targets & ther. 2012;6:277–87. 11. Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Bock A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. The J of allergy and clin immunol. 2004;114(4):936–42. 12. Nicolay U, Kiessling P, Berger M, Gupta S, Yel L, Roifman CM, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26(1):65–72. 13. Fasth A, Nystrom J. Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin. J Clin Immunol. 2008;28(4):370–8. 14. Ducruet T, Levasseur MC, Des Roches A, Kafal A, Dicaire R, Haddad E. Pharmacoeconomic advantages of subcutaneous versus intravenous immunoglobulin treatment in a Canadian pediatric center. The J of allergy and clin immunol. 2013;131(2):585–7. e1-3. 15. Charles C, Gafni A, Whelan T. Decision-making in the physician ± patient encounter: revisiting the shared treatment decision-making model. Soc Sci Med. 1999;49(5):651–61. 16. Stevensona FA, Barry CA, Brittenb N, Barberc N, Bradley CP. Doctor-patient communication about drugs: the evidence for shared decision making. Soc Sci Med. 2000;50(6):829–40.
ASTUTE CLINICIAN REPORT
SCIg vs IVIg: Let’s Give Patients the Choice! K. Samaan & M. C. Levasseur & H. Decaluwe & C. St-Cyr & H. Chapdelaine & A. Des Roches & E. Haddad
Received: 6 January 2014 / Accepted: 13 May 2014 # Springer Science+Business Media New York 2014
Introduction Intravenous immunoglobulins (IVIg) and subcutaneous immunoglobulins (SCIg) are equally efficient in preventing serious bacterial infections (1–5) in patients with primary immune deficiency (PID). Currently, SCIg or IVIG use is often based upon physician’s judgment (2, 6). However, in some centers such as ours, patients are given the choice of treatment modality, regardless of the physician’s opinion on “idealness” of the candidate. In this retrospective study of 143 patients with PID treated by immunoglobulin (Ig) replacement, we present our experience regarding patient’s behavior when given choice of hospital-based IVIg versus home-based SCIg.
Methods We retrospectively analyzed our tertiary center pediatric cohort of 143 patients with PID on Ig replacement. All patients, K. Samaan : M. C. Levasseur : H. Decaluwe : C. St-Cyr : A. Des Roches : E. Haddad (*) Department of Pediatrics, University of Montreal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada e-mail: [email protected] H. Chapdelaine Department of Allergy, University of Montreal, Centre Hospitalier Universitaire de Montreal, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada E. Haddad Department of Microbiology and Immunology, University of Montreal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Chemin de la Cote-Sainte-Catherine, Montreal, QC H3T 1C5, Canada
regardless of the physician and nurse’s impression of the “idealness” of the candidates, were offered the choice between hospital-based IVIg and home-based SCIg. Patients were separated into 2 cohorts: a “switch” cohort of patients already on IVIg when the choice of route of administration was given to them in 2007 when SCIg became available in Quebec, and a “new” cohort, consisting of patients diagnosed thereafter and thus, given the choice at the beginning of Ig replacement. The physician explained both treatment options in general terms and our clinical nurse provided technical explanations on the methods, along with written information describing the modalities and side effects. In all cases, it was clearly indicated that both routes were equally effective. Importantly, it was emphasized that patients had the choice to change their mind at a later point in time if desired and as many times as desired. IVIg was administered in our day treatment center every 4 weeks. SCIg patients received three weekly 2 h sessions with our clinical nurse, before administering SCIg independently at home. Our institution provided patients with infusion tubing and syringes, and pumps were provided by the Ig company. For patients switching from IVIg to SCIg, SCIg injections consisted of 100 % of their IV dose divided over 4 weeks, and started 1 to 2 weeks after the last IVIg infusion. All starting doses of Ig for new patients were calculated on the basis of 400 mg/kg/4 weeks. IV doses were titrated based upon serum IgG trough levels, avoiding trough levels below 700 mg/dl, while SCIg doses were measured 3 months after the initiation of the treatment and then at every 4 months with the same objective. Patients’ demographics characteristics are shown in Table I.
J Clin Immunol Table I Demographic characteristics of patients in each cohort Switch cohort Switching to SCIg Sex male: n (%) Age at diagnosis in years Age of patients when given choice of treatment in years PID diagnosis: n Common variable immunodeficiency Isolated IgG deficiency IgG class 2 deficiency Combined immunodeficiency Di George syndrome HyperIgE Other
29 (57 %) 7.2 10.7 37 3 3 2 1 0 5*
New cohort Staying on IVIg
11
Starting on SCIg 55 (59 %) 7.1 6.0 39 27 4 3 4 3 12□
Starting on IVIg
8.3
*=1X-linked agammaglobulinemia, 2 X-linked lymphoproliferative disorder, 1 NEMO, 1 Rothman-Thompson syndrome □
=1 X-linked agammaglobulinemia, 3 humoral deficiency not otherwise specified, 3 ataxia-telangiectasia, 1 tricho-hepato-intestinal syndrome, 1 polysaccharide antibody deficiency, 1 ALPS-like syndrome with IgG deficiency, 1 congenital dyskeratosis, 1 hyperIgM PID: primary immunodeficiency
Results
Analysis of Compliance
Analysis of the Patients’ Choice
Poor compliance to SCIg was noted in 3 (6 %) patients in the “switch” cohort and in 7 (9 %) in the “new” cohort. Reasons for non compliance were: monoparental families and poor supervision in pre-teenagers and teenagers, attention-deficit disorder in parents or child, and parental stress regarding the SCIg modality. A switch to IVIg was proposed and these patients eventually decided to switch to IVIg. Two of these patients returned to SCIg treatment 2 and 23 months later without any relapse of poor compliance.
Patients’ choices in both cohorts are shown in Fig. 1. In the “switch” cohort (n=51), all patients but 1 chose to switch to SCIg. After an average follow up of 52 months (range 30– 75 months), 44 patients (88 %) remained on SCIg. In the “new” cohort, almost half of patients (44/92) initially chose SCIg with an additional 35/48 later switching from IVIg to SCIg after an average of 6.8 months. Currently, 74 patients (80 %) in the “new” cohort are on SCIg after an average follow up of 33.2 months (range 7.9–66.3 months). Together, only a total of 13 patients switched from SCIg to IVIg. The reasons noted were change in family situation (parental medical difficulties), pain associated with the frequent injections and compliance issues.
Tolerability SCIg was well tolerated without any systemic reaction. Five patients developed local reactions at injection sites, which resolved by 3 months of treatment. Additionally, 2 of these patients developed hypersensitive subcutaneous nodules at injection sites, which resolved when the sites were rotated. In patients on IVIg, side effects were similar to those seen in the literature (7–9). No cases of anaphylaxis occurred in either cohort. The mean steady-state level of IgG was 920 mg/dl (range 600–1250) for patients under IVIg and 900 mg/dl (range 530–1470) for patients under SCIg (p=0.67).
Analysis of Patient’s Behavior When the Choice was Offered Stress in relation to the need to make a choice was assessed by retrospective analysis of medical and nursing notes. Stress was more obvious in patients from the “new” cohort, since 70 and 30 % of patients exhibited a mild stress in the “new” cohort and in the “switch cohort”, respectively. Despite this stress, patients mentioned that they were reassured by being offered the possibility of changing treatment modality as they wanted.
Discussion We have been able to safely and efficiently give our patients the choice between hospital-based IVIg and home-based SCIg. This attitude of giving the choice without preconceived opinions allowed us to be pleasantly surprised by the perfect
J Clin Immunol
a)
44 stayed on SCIg (88%)
1 patient died of neoplasm
6 switched back to IVIg (12%)
1 returned to SCIg
50 chose to switch to SCIg (98%) 51 patients requiring Ig replacement therapy 1 chose to remain on IVIg (2%)
b)
42 stayed on SCIg (95%) 44 starting on SCIg at onset (48%) 2 switched to IVIg (5%)
92 patients requiring Ig replacement therapy 35 switched to SCIg (73%)
5 switched to IVIg (14%)
2 switched to SCIg
48 starting on IVIg (52%) 13 stayed on IVIg (27%)
Fig. 1 Flowchart of patients’ distribution in two cohorts: a Distribution of patients in the “switch” cohort, who were already on Ig replacement when SCIg became available. b Distribution of patients in the “new” cohort who were offered SCIg therapy at time of diagnosis
compliance observed in 5 of 6 patients, who, if the traditional approach of physician’s selection of patients had been followed, would not have been offered the choice, demonstrating that a medical a priori can be false. Also, providing patients with the opportunity to be responsible for their own health could be a factor that diminishes poor compliance. SCIg became the mainstay of treatment in both cohorts, since among the 142 surviving patients currently, 118 (83 %) are under SCIg, suggesting its association with a better quality of life (QoL). Multiple studies have demonstrated that SCIg is associated with a better QoL (6, 10–13) and this could have contributed to the strong preference we observed for SCIg. However, this study does not allow for such a conclusion for various reasons. Firstly, the location of Ig replacement delivery (home versus hospital) was inherently associated with the route of delivery (SC versus IV). It is possible that if IVIg were administered at home, patients would prefer the IV method to the SC method. Unfortunately, it is not possible in our current medical setup in Quebec to provide home-based IVIg. In addition, one cannot rule out the hypothesis that the setup for IVIg in our center is inconvenient and could contribute to the fact that most of the patients switched from IVIg to SCIg. One would have to conduct a multicenter study, and even doing so would not eliminate the potential problem that in some centers, hospital-administered Ig may be unpleasant.
Secondly, written information provided to patients has not been validated prospectively before the study and one could argue that the presentation of treatment modalities could have been biased and that personal beliefs may have contributed to patients’ decision. However, interestingly, in the “new” cohort, approximately half chose IVIg suggesting that the explanations given to patients regarding choice of modality were likely neutral. Since our center provided patients with free material for SCIg infusion, one could argue that this impacted patients’ choices. A pharmacoeconomic study, previously performed in our center, comparing the costs of IVIg and SCIg, showed that the total cost of SCIg was significantly lower than IVIg from hospital, government, insurance companies and patients perspectives (14). In this pharmacoeconomic study, the costs of tubing, syringes and pumps were applied to the parents’ costs (14), meaning that the cost of materials was offset by the savings in loss of productivity and cost of travel. Therefore, it is likely that even if materials were not provided for free, patients would have chosen SCIg more frequently than IVIg, although it would have probably reduced the percentage of patients choosing SCIg. Altogether, we believe that there is no “ideal candidate” for SCIg or IVIG therapy. In the current medical culture, the patient has become a partner (15, 16), and giving the patient the choice for his/her treatment is very apropos. We demonstrate here that giving patients the choice of Ig replacement is a feasible, safe and efficient strategy.
J Clin Immunol Acknowledgments Elie Haddad is a scholar of Fonds de la Recherche en Santé au Québec (FRQS). Funding Funds to hire a native English speaker to help with editing the final version of the manuscript was provided by CSL Behring. The authors did not work for CSL Behring and CSL Behring was not involved in the design of the study or writing of the manuscript.
References 1. Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M, Subcutaneous Ig GSG. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26(3):265–73. 2. Berger M. Choices in IgG replacement therapy for primary immune deficiency diseases: subcutaneous IgG vs. intravenous IgG and selecting an optimal dose. Curr Opin Allergy Clin Immunol. 2011;11(6):532–8. 3. Chapel HM, Spickett GP, Ericson D, Engl W, Eibls MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20(2):94–100. 4. Ballow M. Immunoglobulin therapy: methods of delivery. The J of allergy and clin immunol. 2008;122(5):1038–9. 5. Haddad E, Barnes D, Kafal A. Home therapy with subcutaneous immunoglobulins for patients with primary immunodeficiency diseases. Transfusion and apheresis science : official j of the World Apher Assoc : official j of the Eur Soc for Haemapheresis. 2012;46(3):315–21. 6. Wasserman RL. Progress in gammaglobulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. J Clin Immunol. 2012;32(6):1153–64. 7. Eibl MM. History of immunoglobulin replacement. Immunol Allergy Clin N Am. 2008;28(4):737–64.
8. Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29(3):173–84. 9. Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the primary immunodeficiency committee of the american academy of allergy, asthma and immunology. The J of allergy and clin immunol. 2006;117(4 Suppl):S525– 53. 10. Kobrynski L. Subcutaneous immunoglobulin therapy: a new option for patients with primary immunodeficiency diseases. Biologics : targets & ther. 2012;6:277–87. 11. Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Bock A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. The J of allergy and clin immunol. 2004;114(4):936–42. 12. Nicolay U, Kiessling P, Berger M, Gupta S, Yel L, Roifman CM, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26(1):65–72. 13. Fasth A, Nystrom J. Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin. J Clin Immunol. 2008;28(4):370–8. 14. Ducruet T, Levasseur MC, Des Roches A, Kafal A, Dicaire R, Haddad E. Pharmacoeconomic advantages of subcutaneous versus intravenous immunoglobulin treatment in a Canadian pediatric center. The J of allergy and clin immunol. 2013;131(2):585–7. e1-3. 15. Charles C, Gafni A, Whelan T. Decision-making in the physician ± patient encounter: revisiting the shared treatment decision-making model. Soc Sci Med. 1999;49(5):651–61. 16. Stevensona FA, Barry CA, Brittenb N, Barberc N, Bradley CP. Doctor-patient communication about drugs: the evidence for shared decision making. Soc Sci Med. 2000;50(6):829–40.
