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Monoclonal Antibody Consumption Pattern in a Sponsored Tertiary-Care Healthcare System in a Developing Country: a Five-Year Study from 2013 - 2017

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Monoclonal Antibody Consumption Pattern in a Sponsored Tertiary-Care Healthcare System in a Developing Country: a Five-Year Study from 2013 - 2017 ArchiveJ Arch Mil Medof .SID 2018 September; 6(3):e79185. doi: 10.5812/jamm.79185. Published online 2018 November 17. Research Article Monoclonal Antibody Consumption Pattern in a Sponsored Tertiary-Care Healthcare System in a Developing Country: A Five-Year Study From 2013 - 2017 Inam Danish Khan 1, *, Anantharam Tejus 1, HN Vidyullatha 2, KS Rajmohan 1, Anuradha Makkar 1, Jadhav Amol 1, Narayanan Subhramanian 1, Pragyan Swagatika Panda 1, Manisha Gupta 3, Parwez Parwez 4 and Sikandar Hayat 5 1Army College of Medical Sciences and Base Hospital, New Delhi, India 2Raja Rajeshwari Dental College and Hospital, Bangalore, India 3Sanjay Gandhi Post Graduate Institute, Lucknow, India 4Institute of Human Behaviour and Allied Sciences, New Delhi, India 5Lady Harding Medical College, New Delhi, India *Corresponding author: Associate Professor of Clinical Microbiology and Infectious Diseases, Army College of Medical Sciences and Base Hospital, New Delhi, India. Email: [email protected] Received 2018 May 17; Accepted 2018 November 10. Abstract Background: Monoclonal antibodies are increasingly being employed in oncology, toxicology, infectious diseases and rheuma- tology owing to unmatched efficacy and safety; nevertheless, their usage in developing countries is restricted due to high cost to the exchequer. The newer production line of monoclonal antibodies comes forth with improved efficacy and safety of the current generation monoclonal antibodies and has led to a meteoric growth in their utility. Methods: We performed a comparative analysis of consumption pattern of monoclonal antibodies in a sponsored tertiary-care healthcare system during 2013 - 2017. The humanized anti-IgE monoclonal antibody, omalizumab, was compared with various groups of drugs used for the treatment of bronchial asthma such as combination of long-acting β-agonists and inhaled corticos- teroids, short-acting β-agonists and anticholinergics, and inhaled corticosteroids and leukotriene receptor antagonists. Results: The consumption pattern revealed a three-fold increase in the number of monoclonal antibodies during 2016 - 2017 com- pared to the three-year period from 2013 to 2015. Omalizumab incurred the highest cost burden relative to other medicines used in bronchial asthma. The comparative analysis of usage pattern of monoclonal antibodies, immunomodulators, anti-HIV drugs and all insulin preparations demonstrates annually rising cost burden of monoclonal antibodies. Conclusions: The study showed an increasing trend of healthcare costs and proportionately increasing use of monoclonal anti- bodies, which add to the quality of care through increased efficacy and safety. We need to accept the fact that quality comes with an additional cost burden, and costs can be optimized with economy of scale. Keywords: Monoclonal Antibodies, Immunotherapy, Omalizumab, Efficacy, Drug Safety 1. Background therapeutics has boosted their usage leading to an esti- mated global market value of more than 75 billion USD, Monoclonal antibodies are relatively newer molecules which is expected to scale up to 120 billion USD in future in the armamentarium of modern healthcare, which have years (3). been used as diagnostic and therapeutic agents for ap- proximately 30 years (1,2). In 1986, muromonab CD3, the The idea behind monoclonal antibodies began by Ki- first monoclonal antibody was approved for preventing tasato and Behring, who were successful in curing infec- acute transplant graft rejections, and since then more than tious diseases such as anthrax, diphtheria and tetanus 60 monoclonal antibodies have been approved by United with serum of recovering infected patients referred to States-Food and Drug Administration (US-FDA). More than as ‘Magic bullets’ (4,5). Immunotherapy was success- 70 monoclonal antibodies are being employed in oncol- ful and promising although led to serum sickness in pa- ogy, toxicology, infectious diseases, and rheumatology. tients. This gave impetus to overcome this limitation and Their astound utility and superiority over conventional in 1975, Kohler and Milstein developed a novel technique Copyright © 2018, Journal of Archives in Military Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages,www.SID.ir provided the original work is properly cited. Archive of SID Khan ID et al. to isolate a single clone of antibodies known as mono- munomodulators, anti-HIV drugs and all insulin prepara- clonal antibodies against a particular antigen by fusing B- tions from 2013 to 2017. lymphocytes from the spleen of immunized mice and can- cerous myeloma cells through hybridoma technique (6- 8). Inherent limitations of mouse models are attributable 3. Results to immunogenicity manifesting as hypersensitivity, acute anaphylaxis and pseudoallergic reaction, which have been The consumption pattern revealed a three-fold in- addressed through recombinant technology leading to crease in the number of monoclonal antibodies dur- development of less immunogenic monoclonal antibod- ing 2016 - 2017 compared to the three-year period ies, such as chimeric, humanized and fully human, com- from 2013 to 2015 (Figures 1 and2). The comparative pared to the initial chimeric monoclonal antibodies. Low analysis of omalizumab with other medicines used yield of initial myeloma cell lines and short genetic stabil- in bronchial asthma such as salmeterol-fluticasone, ity through hybridoma techniques have been addressed salbutamol/levosalbutamol-ipratropium bromide for- through Escherichia coli expression systems, transgenic an- mulations, budesonide formulations and montelukast imals, phage display technique and human hybridoma revealed that omalizumab incurred the highest cost bur- technology (1,5,7,9). den amongst them (Figure 3). The comparative analysis of Half-life of polyethylene glycol amalgamation, better usage pattern of monoclonal antibodies, immunomodu- known as PEGylation, has been considerably prolonged by lators, anti-HIV drugs and all insulin preparations demon- improved pharmacokinetics, and genetic engineering has strated an annually rising cost burden of monoclonal helped to considerably improve its specificity, cost, toxic- antibodies (Figure 4). ity and post-effector function (1, 10-13). The newer produc- tion line of monoclonal antibodies comes forth with im- proved efficacy and safety of the current generation mon- oclonal antibodies and has led to a meteoric growth in 9 No of Monoclonal 10 their utility (1,3,5). Despite clinical superiority of mon- Antibodies Utilized in the 8 oclonal antibodies, high cost on the exchequer remains a 5 Hospital 6 3 3 serious limitation in their deployment in frontline health- 4 2 care, especially in developing countries’ healthcare sys- 2 tems, which are under resource limitations and financial 0 2013 2014 2015 2016 2017 austerity. The current ambispective study was undertaken (Till June) Number of Antibodies Used to study the consumption pattern of monoclonal antibod- Year ies in a tertiary-care teaching and research facility under a sponsored healthcare system in a developing country. Figure 1. Use of monoclonal antibodies 2. Methods 4. Discussion The study assessed the consumption pattern of mon- oclonal antibodies in a tertiary-care teaching hospital un- The current study was undertaken to assess the con- der an institutional sponsorship-based healthcare deliv- sumption pattern of monoclonal antibodies as they are ery model over a five-year period (from 2013 to 2017). evolving to become standardized therapeutic regimens The proportional consumption of monoclonal antibod- and they are one of the fastest growing segments of bio- ies was studied for clinical and budgetary analyses utiliz- pharmaceutical industry (3). As brought out by this study, ing suitable clinical comparators. The humanized anti- the number of monoclonal antibodies used has increased IgE monoclonal antibody, omalizumab, was compared exponentially since 2015 (Figure 1). This clearly demon- with various groups of drugs used for the treatment of strates the fact that in recent years monoclonal antibod- bronchial asthma such as combination of long-acting ies are increasingly being employed for the diagnosis and β-agonists and inhaled corticosteroids, short-acting β- therapy of various diseases like cancers, autoimmune dis- agonists and anticholinergics, and inhaled corticosteroids orders and infectious diseases. Monoclonal antibodies and leukotriene receptor antagonists (14, 15). Cost expan- have relatively higher FDA approval rates owing to their sions due to the development of newer drug-delivery mod- efficacy and safety (3). All these factors encourage the de- ules such as inhalers, respules, rotacaps and tablets were velopment of newer monoclonal antibodies in diagnostics included. A comparative analysis was performed in the an- and therapeutics, which furthers the cost-efficacy due to nual consumption pattern of monoclonal antibodies, im- economy of scale. 2 J Arch Mil Med. 2018;www.SID.ir 6(3):e79185. Archive of SID Khan ID et al. 80 2017 70 68.24 2016 60 2015 50 47.78 41.779 2014 40 26.108 2013 30 24.371 17.424 18.195 20 1.869 11.97 15.583 Total Cost in Lakhs Total 7.875 10.192 10 6.416 2.236 0.94 0 0 0 0 0 0 2.119 0 0 00 0 0 Inj Infliximab 100 mg Inj Omalizumab 150 mg Inj Denosumab 120 mg Inj Adalimumab 40 mg Inj Ranibizumab 10 mg / mL Inj Rituximab 500 mgAbciximab
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