|
1
|
Zahari NH, Abd Hamid IJ, Tuan Din SA, Hashim IF, Zainudeen ZT, Mohd Shariff N, Ahmad NH, Tay CY. Practise of Immunoglobulin Replacement Therapy in Primary and Secondary Immunodeficiencies: A Single Centre Experience from Malaysia. Malays J Med Sci 2023; 30:112-121. [PMID: 37425378 PMCID: PMC10325126 DOI: 10.21315/mjms2023.30.3.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 09/25/2022] [Indexed: 07/11/2023] Open
Abstract
Background Intravenous immunoglobulin (IVIG) replacement therapy is increasingly in demand. This study focused on the characteristics of IVIG usage and associated factors toward the frequency status of IVIG among patients in Hospital Kuala Lumpur. Methods A retrospective cross-sectional study was performed on patients who received IVIG in Hospital Kuala Lumpur. Data were extracted from the request forms for IVIG recorded in the Pharmacy Department from January 2018 until December 2019. Chi-squared test and t-test analysis were used for statistical analysis, and a P-value of < 0.05 was considered significant. Results A total of 482 patients received IVIG in Hospital Kuala Lumpur. There were 243 (50.4%) females and 228 (47.3%) males with median age of the patients was 27 years old. The highest indications for IVIG among all patients were hypogammaglobulinemia and other deficiency states in 127 patients (26.3%). The most common indication for one-off treatment in adults was hypogammaglobulinemia and other deficiency states, 35%; whereas in paediatrics, it was Kawasaki disease, 20.3%. The highest indication for regular therapy among adult patients was chronic inflammatory demyelinating polyneuropathy (23.4%), while in paediatrics it was sepsis (31.1%). The clinical category was associated with the frequency status of IVIG usage in both adult and paediatric cohorts with P = 0.004 and P = 0.017, respectively. Conclusion There were significant differences between the indication of one-off treatment and regular therapy among adult and paediatric patients. A national guideline on the prescription of IVIG for patients is instantly needed to help clinicians in prescribing IVIG appropriately.
Collapse
Affiliation(s)
- Nurul Hidayah Zahari
- Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Intan Juliana Abd Hamid
- Primary Immunodeficiency Diseases Group, Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Sharifah Azdiana Tuan Din
- Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Ilie Fadzilah Hashim
- Primary Immunodeficiency Diseases Group, Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Zarina Thasneem Zainudeen
- Primary Immunodeficiency Diseases Group, Department of Clinical Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Noorsuzana Mohd Shariff
- Health Community Department, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Nor Hafizah Ahmad
- Clinical Transfusion Department, National Blood Centre, Kuala Lumpur, Malaysia
| | - Chan Yen Tay
- Pharmacy Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
| |
Collapse
|
|
2
|
Jiao Y, Moll K, Dores GM, Tworkoski E, Zhou CK, Scott D, Wong HL, Fingar K, Burrell T, McEvoy R, Hobbi S, Chillarige Y, Obidi J, MaCurdy T, Kelman J, Shoaibi A. Immune globulin usage trends in commercially insured and Medicare populations, 2009-2019. Transfusion 2023; 63:516-530. [PMID: 36808746 DOI: 10.1111/trf.17261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/09/2022] [Accepted: 12/09/2022] [Indexed: 02/23/2023]
Abstract
BACKGROUND Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life-saving/health-preserving therapy. The study describes US IG utilization patterns from 2009 to 2019. STUDY DESIGN AND METHODS Using IBM MarketScan commercial and Medicare claims data, we examined four metrics overall and by condition-specific categories during 2009-2019: (1) IG administrations per 100,000 person-years, (2) IG recipients per 100,000 enrollees, (3) average annual administrations per recipient, and (4) average annual dose per recipient. RESULTS In the commercial and Medicare populations respectively: IG administrations per 100,000 person-years increased by 120% (213-470) and 144% (692-1693); IG recipients per 100,000 enrollees grew by 71% (24-42) and 102% (89-179); average annual administrations per recipient rose by 28% (8-10) and 19% (8-9); and average annual dose (grams) per recipient increased by 29% (384-497) and 34% (317-426). IG administrations associated with immunodeficiency (per 100,000 person-years) increased by 154% (from 127 to 321) and 176% (from 365 to 1007). Autoimmune and neurologic conditions were associated with higher annual average administrations and dose than other conditions. DISCUSSION IG use increased, coinciding with a growth in the IG recipient population in the United States. Several conditions contributed to the trend, with the largest increase observed among immunodeficient individuals. Future investigations should assess changes in the demand for IVIG by disease state or indication and consider treatment effectiveness.
Collapse
Affiliation(s)
| | | | - Graça M Dores
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| | | | - Cindy Ke Zhou
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| | - Dorothy Scott
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| | - Hui-Lee Wong
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| | | | | | | | - Shayan Hobbi
- IBM Consulting, Bethesda, Maryland, USA
- Accenture Federal Services, Arlington, Virginia, USA
| | | | - Joyce Obidi
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| | - Thomas MaCurdy
- Acumen LLC, Burlingame, California, USA
- Department of Economics, Stanford University, Stanford, California, USA
| | - Jeffrey Kelman
- Centers for Medicare & Medicaid Services, Washington, DC, USA
| | - Azadeh Shoaibi
- Food and Drug Administration, Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA
| |
Collapse
|
|
3
|
Lee JL, Mohd Saffian S, Makmor-Bakry M, Islahudin F, Alias H, Ali A, Mohamed Shah N. Prescribing Practices of Intravenous Immunoglobulin in Tertiary Care Hospitals in Malaysia: A Need for a National Guideline for Immunoglobulin Use. Front Pharmacol 2022; 13:879287. [PMID: 35754485 PMCID: PMC9218597 DOI: 10.3389/fphar.2022.879287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 05/20/2022] [Indexed: 11/13/2022] Open
Abstract
Rational use of drug involves the use of medicine as per clinical guidelines. Given the steady increase in the clinical utility of intravenous immunoglobulin (IVIG) either as licensed or off-label use, concerns are being raised about the possibility of supply shortages that could significantly impact patient care. Therefore, there is a need to regulate and to promote the rational use of this valuable medication. This cross-sectional chart review study attempts to evaluate the prescribing patterns of IVIG at two tertiary hospitals in Malaysia. Patients' medical files and dispensing records were examined and compared with current guidelines. A total of 348 prescriptions for IVIG were written during the 1-year study period. The highest usage of IVIG was for neurological (47.9%), immunological (27.5%), and hematological conditions (20%). The number of prescriptions with the US Food and Drug Administration (FDA) licensed indications and off-label indications was 148 (42.5%) and 200 (57.5%), respectively. Age (OR: 1.02, 95% CI: 1.01-1.03, p = 0.003) and those admitted to the critical care units (OR: 11.11, 95% CI: 5.60-22.05, p < 0.001) were significant factors for receiving IVIG for an off-label indication. Most prescriptions (79%) had appropriate dosing. Significant factors associated with receiving inappropriate dose of IVIG include age (OR: 0.93, 95% CI: 0.89-0.97, p = 0.001) and those admitted to the critical care units (OR: 10.15, 95% CI: 3.81-27.06, p < 0.001). This study advocates the development and implementation of evidence-based clinical guidelines with prioritization protocol to ensure rational use of IVIG.
Collapse
Affiliation(s)
- Jian Lynn Lee
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Department of Pharmacy, Tengku Ampuan Rahimah Hospital, Ministry of Health Malaysia, Selangor Darul Ehsan, Malaysia
| | - Shamin Mohd Saffian
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Mohd Makmor-Bakry
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Farida Islahudin
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Hamidah Alias
- Department of Pediatrics, UKM Medical Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Adli Ali
- Department of Pediatrics, UKM Medical Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Noraida Mohamed Shah
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| |
Collapse
|
|
4
|
Gavrilova N, Kamaeva E, Ignatova M, Ryabkova V, Lukashenko M, Churilov L, Shoenfeld Y. Intravenouse immunoglobuline in dysautonomia. Clin Immunol 2022; 240:109039. [DOI: 10.1016/j.clim.2022.109039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 04/01/2022] [Accepted: 05/07/2022] [Indexed: 11/03/2022]
|
|
5
|
Danieli MG, Verga JU, Mezzanotte C, Terrenato I, Svegliati S, Bilo MB, Moroncini G. Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients. Front Immunol 2022; 12:805705. [PMID: 35111165 PMCID: PMC8801806 DOI: 10.3389/fimmu.2021.805705] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 12/27/2021] [Indexed: 12/27/2022] Open
Abstract
Background Immunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings. Aim This study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra®, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile. Results Results support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidated Conclusions This study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients’ quality of life.
Collapse
Affiliation(s)
- Maria Giovanna Danieli
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.,Clinica Medica, Department of Internal Medicine, Ospedali Riuniti, Ancona, Italy
| | - Jacopo Umberto Verga
- Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.,The Science Foundation Ireland (SFI) Centre for Research Training in Genomics Data Science, National University of Ireland, Galway, Ireland
| | - Cristina Mezzanotte
- Internal Medicine Residency Program, Marche Polytechnic University, Ancona, Italy
| | - Irene Terrenato
- Biostatistics and Bioinformatic Unit, Scientific Direction, IRCCS Regina Elena Cancer Institute, Rome, Italy
| | - Silvia Svegliati
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy
| | - Maria Beatrice Bilo
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.,Allergy Unit, Department of Internal Medicine, Ospedali Riuniti, Ancona, Italy
| | - Gianluca Moroncini
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.,Clinica Medica, Department of Internal Medicine, Ospedali Riuniti, Ancona, Italy
| |
Collapse
|
|
6
|
Kan AKC, Leung GMK, Chiang V, Au EYL, Lau CS, Li PH. Ten-year population trends of immunoglobulin use, burden of adult antibody deficiency and feasibility of subcutaneous immunoglobulin (SCIg) replacement in Hong Kong Chinese. Front Immunol 2022; 13:984110. [PMID: 36591300 PMCID: PMC9795180 DOI: 10.3389/fimmu.2022.984110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022] Open
Abstract
Background Adult antibody deficiency remains under-recognised and under-studied - especially among Asian populations. Patterns of immunoglobulin use and the feasibility of subcutaneous immunoglobulin (SCIg) replacement among Chinese patients remains unclear. Objective To investigate the trends of immunoglobulin use, burden of adult antibody deficiency and the outcomes of patients on SCIg compared to intravenous immunoglobulin (IVIg) replacement in Hong Kong through a retrospective observational study. Methods Population-wide data of immunoglobulin recipients in Hong Kong between 2012 and 2021, and longitudinal clinical data of adult immunodeficiency patients at Queen Mary Hospital were collected and analysed. Results Total immunoglobulin consumption and recurrent immunoglobulin recipients increased continuously from 175,512g to 298,514g (ρ=0.99, p<0.001) and 886 to 1,508 (ρ=0.89, p=0.001) between 2012-21 in Hong Kong. Among 469 immunoglobulin recipients at Queen Mary Hospital in 2021, 344 (73.3%) were indicated for replacement. Compared to those on IVIg (n=14), patients on SCIg replacement (n=8) had fewer immunodeficiency-related hospitalisations (IRR=0.11) and shorter duration of hospitalisation stay (IRR=0.10) per year, as well as better quality of life (SF-36v2 Health Survey and Life Quality Index). Estimated annual healthcare cost of SCIg replacement per patient was lower than that of IVIg (HKD196,850 [USD25,096] vs HKD222,136 [USD28,319]). Conclusion There was a significantly increasing burden of adult antibody deficiency and immunoglobulin consumption in Hong Kong. SCIg was feasible and more cost-effective when compared to IVIg, with SCIg patients experiencing better clinical outcomes and quality of life. Future prospective studies to confirm the long-term efficacy and superiority of SCIg are required.
Collapse
Affiliation(s)
- Andy Ka Chun Kan
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Garret Man Kit Leung
- Division of Haematology, Medical Oncology and Haemopoietic Stem Cell Transplantation, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Valerie Chiang
- Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China
| | - Elaine Yuen Ling Au
- Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China
| | - Chak Sing Lau
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Philip Hei Li
- Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- *Correspondence: Philip Hei Li,
| |
Collapse
|
|
7
|
Koo Y, Yun T, Chae Y, Lee D, Choi D, Oh J, Kim J, Kim H, Yang MP, Kang BT. Suspected human intravenous immunoglobulin-induced acute haemolytic anaemia in a dog. J Small Anim Pract 2021; 63:482-485. [PMID: 34874062 DOI: 10.1111/jsap.13449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 10/18/2021] [Accepted: 10/31/2021] [Indexed: 11/28/2022]
Abstract
A 2-year-old mixed breed dog presented with a 1-year history of crust and erosion on the nasal planum. Because histopathological examination revealed ruptured intraepidermal pustules and superficial dermal inflammation, the dog was diagnosed with pemphigus foliaceus. Human intravenous immunoglobulin was administered in two consecutive doses of 0.5 g/kg/day due to poor therapeutic response to previous immunosuppressive therapy. From Day 3 after the first dose of human intravenous immunoglobulin, tachypnoea, pale mucous membrane, haemoglobinuria and haemoglobinemia were observed, thus confirming haemolytic anaemia. Other drug-induced haemolytic anaemias were excluded because no additional drugs had been administered before the haemolysis occurred. Immune-mediated haemolytic anaemia was also excluded because the direct antiglobulin test was negative. Two transfusions were performed, and haemolysis was not observed from Day 4 of haemolytic anaemia onset. In conclusion, human intravenous immunoglobulin-induced haemolytic anaemia should be considered in dogs that develop haemolysis following the administration of human intravenous immunoglobulin.
Collapse
Affiliation(s)
- Y Koo
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - T Yun
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Y Chae
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - D Lee
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - D Choi
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - J Oh
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - J Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - H Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - M P Yang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - B T Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| |
Collapse
|
|
8
|
Ohad M, Shemer A, Lavie I, Ozeri D, Shoenfeld Y, Kivity S. Intravenous Immunoglobulin for Inflammatory Myositis: Experience in a Tertiary Medical Center. J Clin Rheumatol 2021; 27:e616-e621. [PMID: 32501943 DOI: 10.1097/rhu.0000000000001418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Inflammatory myopathies are treated with glucocorticoids and other immunosuppressive medications. Intravenous immunoglobulin (IVIG) is increasingly used for refractory or severe cases; however, the evidence for their effectiveness is limited. We assessed effectiveness and safety of IVIG when used with other immunomodulatory agents in the treatment of inflammatory myopathies. METHODS This study reviewed records of patients diagnosed with dermatomyositis or polymyositis and treated with IVIG, from 2009 through 2016 in 1 tertiary medical center. Mixed-effects general linear regression models were applied to determine effectiveness of treatment on muscle strength, creatinine phosphokinase levels, and steroid dosage. RESULTS Twenty-three patients with dermatomyositis/polymyositis treated with IVIG were followed up for a mean of 31 (SD, ±25) months. During this period, a significant improvement in muscle strength was demonstrated, with a mean increase of 0.92 Medical Research Council scale points (β = 0.14; confidence interval [CI], 0.136-0.149; p < 0.0001), a significant reduction of creatinine phosphokinase levels and steroid dosage with a mean decrease of 1140 IU/L (β = -0.274; CI, -0.354 to -0.195; p < 0.0001), and 36 mg/d (β = -0.008; CI, -0.011 to -0.006; p < 0.0001), respectively. Overall, remission was observed in 10 patients (43.5%), and partial remission in 6 patients (26%), whereas 1 patient (17%) remained refractory to treatment, and 6 patients (27%) were lost to follow-up. CONCLUSIONS The majority of patients with inflammatory myopathies experienced a clinical and laboratory improvement during IVIG treatment. In addition, a steroid-sparing effect was noticed in most patients. These results encourage the use of IVIG as an alternative treatment option for patients with limited responsiveness to conventional methods.
Collapse
Affiliation(s)
- Maayan Ohad
- From the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
| | | | - Inbar Lavie
- From the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
| | | | | | | |
Collapse
|
|
9
|
Goswami RP, Haldar SN, Chatterjee M, Vij P, van der Kooi AJ, Lim J, Raaphorst J, Bhadu D, Gelardi C, Danieli MG, Kumar U. Efficacy and safety of intravenous and subcutaneous immunoglobulin therapy in idiopathic inflammatory myopathy: A systematic review and meta-analysis. Autoimmun Rev 2021; 21:102997. [PMID: 34800685 DOI: 10.1016/j.autrev.2021.102997] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 11/06/2021] [Accepted: 11/14/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To perform a systematic review and meta-analysis on the efficacy and safety of intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin (Ig) therapy in the treatment of idiopathic inflammatory myopathy (IIM) and juvenile dermatomyositis (JDM). METHODS PubMed, Embase and SCOPUS were searched to identify studies on Ig therapy in patients with IIM and/or JDM (2010-2020). Outcome measures were complete response (CR) or partial response (PR) in terms of muscle power and extramuscular disease activity measures on the International Myositis Assessment and Clinical Studies Group (IMACS) core set domains. RESULTS Twenty-nine studies were included (n = 576, 544 IIM, 32 JDM). Muscle power PR with pooled Ig therapy was 88.5% (95% confidence interval (CI): 80.6-93.5, n = 499) and PR with SCIg treatment was 96.61% (95% CI: 87.43-99.15, n = 59). Pooled PR with first-line use of IVIg was 77.07% (95% CI: 61.25-92.89, n = 80). Overall, mean time to response was 2.9 months (95% CI: 1.9-4.1). Relapse was seen in 22.76% (95% CI: 14.9-33). Studies on cutaneous disease activity and dysphagia showed significant treatment responses. Glucocorticoid and immunosuppressant sparing effect was seen in 40.9% (95% CI: 20-61.7) and 42.2% (95% CI: 20.4-64.1) respectively. Ig therapy was generally safe with low risk of infection (1.37%, 95% CI: 0.1-2.6). CONCLUSIONS Add-on Ig therapy improves muscle strength in patients with refractory IIM, but evidence on Ig therapy in new-onset disease and extramuscular disease activity is uncertain.
Collapse
Affiliation(s)
- Rudra Prosad Goswami
- Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India.
| | - Soumendra Nath Haldar
- Department of Medicine and Microbiology, All India Institute of Medical Sciences, New Delhi, India.
| | - Moumita Chatterjee
- Department of Mathematics and Statistics, Aliah University, Kolkata, India.
| | - Pallavi Vij
- Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India.
| | - Anneke J van der Kooi
- Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100DD Amsterdam, the Netherlands.
| | - Johan Lim
- Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100DD Amsterdam, the Netherlands.
| | - Joost Raaphorst
- Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, PO Box 22660, 1100DD Amsterdam, the Netherlands.
| | - Danveer Bhadu
- Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India.
| | - Chiara Gelardi
- Emergency Medicine, AziendaOspedaliera Marche Nord, Fano, PU 61032, Italy
| | - Maria Giovanna Danieli
- Clinica Medica, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Torrette di Ancona 60020, Italy.
| | - Uma Kumar
- Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India.
| |
Collapse
|
|
10
|
Danieli MG, Piga MA, Paladini A, Longhi E, Mezzanotte C, Moroncini G, Shoenfeld Y. Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease. Scand J Immunol 2021; 94:e13101. [PMID: 34940980 PMCID: PMC8646640 DOI: 10.1111/sji.13101] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/31/2021] [Accepted: 09/08/2021] [Indexed: 12/15/2022]
Abstract
The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called 'cytokines storm' is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg). We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome. The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies' limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.
Collapse
Affiliation(s)
- Maria Giovanna Danieli
- Clinica Medica, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di Ancona and DISCLIMOUniversità Politecnica delle Marche, Clinica MedicaAnconaItaly
- School of Specialisation in Allergology and Clinical Immunology, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di AnconaUniversità Politecnica delle MarcheAnconaItaly
| | - Mario Andrea Piga
- School of Specialisation in Allergology and Clinical Immunology, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di AnconaUniversità Politecnica delle MarcheAnconaItaly
| | - Alberto Paladini
- School of Specialisation in Internal Medicine, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di AnconaUniversità Politecnica delle MarcheAnconaItaly
| | - Eleonora Longhi
- Scuola di Medicina e ChirurgiaAlma Mater StudiorumUniversità degli Studi di BolognaBolognaItaly
| | - Cristina Mezzanotte
- School of Specialisation in Internal Medicine, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di AnconaUniversità Politecnica delle MarcheAnconaItaly
| | - Gianluca Moroncini
- Clinica Medica, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di Ancona and DISCLIMOUniversità Politecnica delle Marche, Clinica MedicaAnconaItaly
- School of Specialisation in Internal Medicine, Dipartimento di Medicina Interna, AOU Ospedali Riuniti di AnconaUniversità Politecnica delle MarcheAnconaItaly
| | - Yehuda Shoenfeld
- Ariel UniversityArielIsrael
- The Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterRamat GanIsrael
- Saint Petersburg State UniversitySt. PetersburgRussia
- I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)MoscowRussia
| |
Collapse
|
|
11
|
Brand A, De Angelis V, Vuk T, Garraud O, Lozano M, Politis D. Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand. Transfus Clin Biol 2021; 28:96-122. [PMID: 33321210 DOI: 10.1016/j.tracli.2020.12.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety. By contrast, the producers of PDMPs have developed pathogen reduction techniques for inactivating the microorganisms in (pooled) plasma, but little attention has been paid to the pertinence of the clinical indications for these products. The use of blood, and of erythrocytes in particular, has declined by almost 40%, but the use of immunoglobulins (IG) tripled between 2004 and 2018, making it necessary to pay donors to obtain sufficient blood to meet the market demand for these products. We analyzed the reasons for this increase to unsustainable levels of use, by investigating (practice) guidelines, recommendations, Cochrane data analyses and systematic reviews for clinical indications for IG over time. We found no new evidence explaining the huge increase up to 2018 or the predicted 5-7% yearly annual increase until 2024. For some former evidence-based indications, biologics have largely replaced IG, but the administration of IG for doubtful indications (up to 40%) has not decreased in recent decades. The main development since 2004 is that IG use in Europe has become market-driven rather than evidence-guided. As transfusion specialists and blood therapists, we must raise the alarm that this situation is likely to continue in the absence of good clinical studies determining the place of IG alongside other treatments, and for as long as market profitability remains the dominant driving force. We discuss here approaches for reversing this trend and moving towards European self-sufficiency through non-remunerated voluntary blood donation.
Collapse
Affiliation(s)
- A Brand
- Sanquin Research, Center for Clinical Transfusion Research, Leiden and Jon J van Rood Center for Clinical Transfusion Science, Leiden University Medical Center, 2333 Leiden, the Netherlands.
| | | | - T Vuk
- Croatian Institute of Transfusion Medicine, 10000 Zagreb, Croatia
| | - O Garraud
- Inserm_1059, University of Lyon-Saint-Étienne, Saint-Étienne, France; Institut National de la Transfusion Sanguine, 75015 Paris, France
| | - M Lozano
- Department of Hemotherapy and Hemostasis. ICMHO, University Clinic Hospital, IDIBAPS, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - D Politis
- Coordinating Centre for Hemovigilance and Surveillance of Transfusion (SKAEM) of the Hellenic National Public Health Centre, Agravon street 3-5, 15123 Marousi, Greece
| |
Collapse
|
|
12
|
Alsaleem M. Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review. Antibodies (Basel) 2020; 9:E60. [PMID: 33158209 PMCID: PMC7709108 DOI: 10.3390/antib9040060] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/07/2020] [Accepted: 11/02/2020] [Indexed: 02/07/2023] Open
Abstract
Intravenous immune globulin (IVIG) is made after processing plasma from healthy donors. It is composed mainly of pooled immunoglobulin and has clinical evidence-based applications in adult and pediatric populations. Recently, several clinical applications have been proposed for managing conditions in the neonatal population, such as hemolytic disease of the newborn, treatment, and prophylaxis for sepsis in high-risk neonates, enterovirus parvovirus and COVID-19 related neonatal infections, fetal and neonatal immune-induced thrombocytopenia, neonatal hemochromatosis, neonatal Kawasaki disease, and some types of immunodeficiency. The dosing, mechanism of action, effectiveness, side effects, and adverse reactions of IVIG have been relatively well studied in adults but are not well described in the neonatal population. This review aims to provide the most recent evidence and consensus guidelines about the use of IVIG in the fetus and neonate.
Collapse
Affiliation(s)
- Mahdi Alsaleem
- Pediatrics Department, Neonatology, Children’s Mercy Hospital, Kansas City, MO 64108, USA;
- Pediatrics Department, University of Kansas, Wichita, KS 67208, USA
| |
Collapse
|
|
13
|
Subcutaneous immunoglobulin in inflammatory myopathies: efficacy in different organ systems. Autoimmun Rev 2019; 19:102426. [PMID: 31734407 DOI: 10.1016/j.autrev.2019.102426] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 07/26/2019] [Indexed: 12/12/2022]
Abstract
MGD and CG were responsible for the study's conception and design. VP and DM contributed to data acquisition. VP and DB planned and performed the statistical analyses. All Authors contributed to data interpretation. MGD, CG, VP and DM drafted the manuscript. AG and DB revised the manuscript critically for intellectual content. All authors gave their final approval of the version of the manuscript to be published.
Collapse
|
|
14
|
Horwitz DA, Fahmy TM, Piccirillo CA, La Cava A. Rebalancing Immune Homeostasis to Treat Autoimmune Diseases. Trends Immunol 2019; 40:888-908. [PMID: 31601519 DOI: 10.1016/j.it.2019.08.003] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 08/01/2019] [Accepted: 08/14/2019] [Indexed: 12/18/2022]
Abstract
During homeostasis, interactions between tolerogenic dendritic cells (DCs), self-reactive T cells, and T regulatory cells (Tregs) contribute to maintaining mammalian immune tolerance. In response to infection, immunogenic DCs promote the generation of proinflammatory effector T cell subsets. When complex homeostatic mechanisms maintaining the balance between regulatory and effector functions become impaired, autoimmune diseases can develop. We discuss some of the newest advances on the mechanisms of physiopathologic homeostasis that can be employed to develop strategies to restore a dysregulated immune equilibrium. Some of these designs are based on selectively activating regulators of immunity and inflammation instead of broadly suppressing these processes. Promising approaches include the use of nanoparticles (NPs) to restore Treg control over self-reactive cells, aiming to achieve long-term disease remission, and potentially to prevent autoimmunity in susceptible individuals.
Collapse
Affiliation(s)
- David A Horwitz
- General Nanotherapeutics, LLC, Santa Monica, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| | - Tarek M Fahmy
- Department of Biomedical Engineering, School of Engineering and Applied Sciences, Yale University, New Haven, CT, USA; Chemical and Environmental Engineering, School of Engineering and Applied Sciences, Yale University, New Haven, CT, USA; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA
| | - Ciriaco A Piccirillo
- Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada; Program in Infectious Disease and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montréal, QC, Canada; Centre of Excellence in Translational Immunology (CETI), Research Institute of the McGill University Health Centre, Montréal, QC, Canada
| | - Antonio La Cava
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| |
Collapse
|