Pattern of complications and burden of disease in patients affected by beta thalassemia major

Abstract

Objectives: Despite the correct application of blood transfusions and chelation treatments, beta thalassemia patients have many complications. Systematic population analyses on types and frequency of these complications are very few. The aim of this study is to characterize the complications, their risk factors and their clinical and economic impact.

Methods: Complications at baseline and events occurring during one observational year were analyzed in 272 patients aged >12 years. Risk factors were analyzed through chi-squared and unpaired t tests. Logistic regression was applied to perform the risk factors multivariate analysis.

Results: A total of 554 complications (1–6 per patient) affected 82.3% of patients. Cardiac complications were less represented than expected. Musculoskeletal diseases were the most represented complications followed by hepatic, sexual and endocrine diseases. Splenectomized patients, born before 1970 and aged >40 years, starting iron chelation therapy when aged >4 years or after receiving more than 20 blood transfusions, presented a significantly higher number of complications. A total of 885 adverse events requiring 34125 additional medical services occurred in 1 year. Of these, 34.9% were related to treatments and 65.1% to other causes. Event numbers, additional medical interventions and cost increased progressively in patients affected by one or more complication compared to patients with no complications.

Conclusions: The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.

Keywords:

• Thalassemia
• complications
• adverse reactions
• risk factors
• cost of the disease

Transparency

Declaration of funding

This manuscript has been published on behalf of the HTA-THAL project, funded by the < grant sponsor > Ministry of Health, Italy</grant sponsor> (art 12 D.LGS. 502/1992) and cofunded by the Fondazione Giambrone.

Author contributions: All authors fulfill the authorship criteria and contributed as following described: F.B. designed the research study, evaluated data and wrote the manuscript. R.C. analyzed the data and wrote the manuscript. P.B. performed the statistical analysis and collaborated on data evaluation. D.B. designed the research study and commented on the manuscript. M.F. analyzed the data and commented on the manuscript. P.G. collaborated on data collection and commented on the manuscript. V.G. collaborated on research study design and commented on the manuscript. A.I. provided comments from the patients’ point of view and collaborated on data collection and evaluation. R.P. collaborated on research study design, data collection and evaluation. A.P. collaborated on data collection and commented on the manuscript. M.C.P. collaborated on data collection and commented on the manuscript. L.R. supported the data analysis and the writing of the manuscript. G.C.D.V. collaborated on data analysis and evaluation and commented on the manuscript. A.F. collaborated on data analysis and evaluation and commented on the manuscript. A.M. collaborated on data collection and commented on the final version of the manuscript. A.C. designed the research study, analyzed the data and provided the final version of the manuscript.

Fedele Bonifazi^a, Rosa Conte^a, Paola Baiardi^b, Donato Bonifazi^c, Mariagrazia Felisi^c, Paola Giordano^d, Viviana Giannuzzi^a, Angela Iacono^e, Rosa Padula^c, Alessia Pepe^f, Maria Caterina Putti^g, Lucia Ruggieri^a, Giovanni Carlo Del Vecchio^h, Aldo Filosaⁱ, Aurelio Maggio^j and Adriana Ceci^a

Declaration of financial/other relationships

A.P. is the scientific coordinator of the MIOT (Myocardial Iron Overload in Thalassemia) and E-MIOT (Extension-MIOT) Networks. A.P. has disclosed that MIOT and E-MIOT received “no profit” support from Chiesi Spa, Apopharma Inc. and Bayer. F.B., R.C., P.B., D.B., M.G.F., P.G., V.G., A.I., R.P., M.C.P., L.R., G.C.D.V., A.F., A.M. and A.C. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors wish to thank Fondazione Giambrone for its contribution.