Antibodi Monoklonal Anti-CD3 Sebagai Terapi Diabetes Mellitus Tipe 1: Sebuah Kajian Sistematis dan Meta-analisis
DOI:
https://doi.org/10.29303/jku.v10i3.580Kata Kunci:
Anti-CD3, Diabetes Mellitus Tipe 1, HbA1C, Insulin, Peptida CAbstrak
Abstrak
Latar belakang: Diabetes mellitus tipe 1 (T1DM) merupakan penyakit autoimun kronis yang ditandai dengan peningkatan akdar glukosa darah yang persisten (hiperglikemia). Utamanya diderita oleh anak berusia <15 tahun, T1DM membuat penderitanya menjadi bergantung kepada terapi insulin eksogen sepanjang hidupnya. Kemampuan antibodi monoklonal anti-CD3 untuk menurunkan aktivasi sel T namun masih menjaga kemampuan immunomodulatorisnya membuat modalitas terapi ini menjadi modalitas yang menjanjikan. Meta-analisis ini bertujuan untuk menginvestigasi efek pemberian antibodi monoklonal anti-CD3 pada pasien diabetes mellitus tipe 1.
Metode: Kajian sistematik dilakukan dengan mengikuti kaidah PRISMA dengan menggunakan pusat data daring yaitu PubMed, ScienceDirect, dan Cochrane. Studi yang menilai efek dari terapi antibodi monoklonal anti-CD3 pada pasien diabetes mellitus tipe 1 serta sesuai dengan kriteria inklusi dilibatkan dalam kajian sistemaik ini. Risiko bias setiap studi inklusi dinilai menggunakan kriteria CONSORT. Meta-analisis dengan metode random-effects selanjutnya dilakukan untuk mendapatkan Mean Difference (MD) gabungan dari seluruh studi inklusi beserta dengan 95% Confidence Interval (CI).
Hasil: 10 studi yang melibatkan 1458 dilibatkan dalam kajian sistematik ini,. Ditemukan bahwa terapi anitbodi monoklonal anti-CD3 mampu menurunkan dosis kebutuhan insulin (MD -0.18 [95% CI: -0.22, -0.13],I2=59%, p<0,0001) dan kadar HbA1c (MD -0.71[95% CI: -1.18, -0.24], I2=78%, p=0.003). Selain itu, ditemukan juga bahwa terapi ini mampu meningkatkan respon peptida C
Kesimpulan: Terapi antibodi monoklonal anti-CD3 menunjukkan efek positif terhadap kebutuhan insulin, kadar HbA1c, dan respon peptida C pada pasien diabetes mellitus tipe 1
Referensi
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J. C. Ozougwu, K. C. Obimba, C. D. Belonwu and C. B. Unakalamba, "The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus," academicJournals, vol. 4, no. 4, pp. 46-57, 2013.
L. Lucaccioni and L. Iughetti, "Issues in Diagnosis and Treatment of Type 1 Diabetes Mellitus in Childhood," Journal of Diabetes Mellitus, vol. 6, pp. 175-183, 2016.
B. Saberzadeh-Ardestani, R. Karamzadeh, M. Basiri, E. Hajizadeh-Saffar, A. Farhadi, J. Shapiro, Y. Tahamtani and H. Baharvand, "Type 1 Diabetes Mellitus: Cellular and Molecular Pathophysiology at A Glance," Cell J, vol. 20, no. 3, pp. 294-301, 2018.
A. Iqbal, P. Novodvorsky and S. R. Heller, "Recent Updates on Type 1 Diabetes Mellitus Management for Clinicians," Diabetes & Metabolic Journal, vol. 42, pp. 3-18, 2018.
American Diabetes Association, "Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2020," Diabetes Care, vol. 43, no. 1, pp. 598-5110, 2020.
X. Luo, K. Herold and S. Miller, "Immunotherapy of Type 1 Diabetes – Where are We At and," Immunity, vol. 32, no. 4, April 2010.
A. Kaufman and K. Herold, "Anti-CD3 mAbs for treatment of type 1 diabetes," DIABETES/METABOLISM RESEARCH AND REVIEWS, vol. 25, March 2009.
J. Gaglia and S. Kissler, "Anti-CD3 antibody for the prevention of type 1 diabetes - a story of perseverance," Biochemistry, vol. 58, no. 40, October 2019.
K. Herold, W. Hagopian, J. A. Auger, E. Poumian-Ruiz, L. Taylor, D. Donaldson, S. Gitelman, D. M. Harlan, D. Xu, R. A. Zivin and J. A. Bluestone, "Anti CD-3 Monoclonal Antibody in New- Onset Type 1 Diabetes Mellitus," The New England Journal of Medicine, vol. 346, no. 22, 2002.
R. D. Riley, K. G. Moons , K. I. E. Snell, J. Ensor, L. Hooft, D. G. Altman, J. Hayden, G. S. Collins and t. P. A. Debray , "A guide to systematic review and meta-analysis of prognostic factor studies," BMJ, vol. 364, p. k4597, 2019.
J. P. T. Higgins, S. G. Thompson, J. J. Deeks and D. G. Altman, "Measuring inconsistency in meta-analyses," BMJ, vol. 327, p. 557, 2003.
A. Janez, C. Guja , A. Mitrakou, N. Latic , T. Tankova , L. Czupryniak, A. G. Tabak, M. Prazny, E. Martinka and L. S. Duvnjak, "Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review," Diabetes Therapy, vol. 11, no. 11, pp. 387-409, 2020.
L. A. DiMeglio, C. E. Molina and R. A. Oram, "Type 1 diabetes," Lancet, vol. 391, no. 10138, pp. 2449-2462, 2019.
C. K. Cheon, "Understanding of type 1 diabetes mellitus: what we know and where we go," Korean Journal of Pediatrics, vol. 61, no. 10, pp. 307-314, 2018.
K. M. Simmons and A. W. Michels , "Type 1 diabetes: A predictable disease," World Journal of Diabetes, vol. 6, no. 3, pp. 380-390, 2015.
J. Lebastchi, S. Deng, A. H. Lebastchi, I. Beshar, S. Gitelman, S. Willi, P. Gottlieb, E. M. Akirav, A. J. Bluestone and K. C. Herold, "Immune Therapy and B-cell Death in Type 1 Diabetes," Diabetes Journal, vol. 62, pp. 1676-1680, 2013.
K. C. Herold, S. E. Gitelman, M. R. Ehlers, P. A. Gottlieb, C. J. Greenbaum, W. Hagopian, K. D. Boyle, L. Keyes-Elstein, S. Aggarwal, D. Phippard, P. H. Sayre, J. McNamara and J. A. Bluestone, "Teplizumab (Anti-CD3 mAb) Treatment Preserves C-Peptide Responses in Patients With New-Onset Type 1 Diabetes in a Randomized Controlled Trial," Diabetes Journal, vol. 62, pp. 3766-3774, 2013.
W. Hagopian , R. J. Ferry, N. Sherry , D. Carlin, E. Bonvini, S. Johnson, K. E. Stein , S. Koenig, A. G. Daifotis, K. C. Herold and J. Ludvigsson, "Teplizumab Preserves C-Peptide in Recent-Onset Type-1 Diabetes," Diabetes, vol. 62, pp. 3901-3908, 2013.
N. Sherry , W. Hagopian, J. Ludvigsson , S. M. Jain , J. Wahlen, R. Ferry, B. Bode, S. Aronoff, C. Holland , D. Carlin, R. Wilder , K. King, S. Pillemer, E. Bonvini , K. Stein, S. Koenig, K. C. Herold and A. Daifotis , "Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year result from a randomised, placebo-controlled trial," Lancet , vol. 378, no. 11, pp. 487-497, 2013.
K. C. Herold, S. Gitelman, C. Greenbaum, J. Puck, W. Hagopian, P. Gottlieb, P. Sayre, P. Bianchine, E. Wong, V. Seyfert-Margolis, K. Bourcier and J. A. Bluestone, "Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years," Clinical Immunology, vol. 132, no. 2, pp. 166-173, 2009.
S. Demeester, B. Keymeulen, L. Kaufman, A. V. Dalem, E. V. Balti, U. V. d. Velde, Patrick Goubert, K. Verhaeghen, H. M. Davidson, J. Wenzlau, I. Weets, D. Pipeleers and F. Gorus, "Preexisting Insulin Autoantibodies Predict Efficacy of Otelixizumab in Preserveing Residual B-cel Function in Recent-Onset Type 1," Diabetes Care, vol. 38, pp. 644-651, 2015.
S. L. Sherwani, H. A. Khan, A. Ekhzaimy, A. Masood and M. K. Sakharkar , "Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients," Biomarker Insights, vol. 11, pp. 95-104, 2016.
B. Mianowska , W. Fendler , A. Szadkowska, A. Baranowska , E. G. Agaciak , J. Sadon, H. Keenan and W. Mlynarski, "HbA1c levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions," Diabetologia, vol. 54, no. 4, pp. 749-756, 2011.
C. Florkowski, "HbA1c as a Diagnostic Test for Diabetes Mellitus – Reviewing the Evidence," The Clinical Biochemist Reviews, vol. 34, no. 2, pp. 75-83, 2013.
K. C. Herold, W. Hagopian, J. A. Auger, E. Poumian-Ruiz, L. Taylor, D. Donaldson, S. E. Gitelman, D. M. Harlan, D. Xu, R. A. Zivin and J. A. Bluestone, "Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus," The New England Journal of Medicine, vol. 346, no. 22, pp. 1692-1698, 2002.
K. C. Herold, S. E. Gitelman, M. Umesh, W. Hagopian, B. Bisikirska, D. Donaldson, K. Rother, B. Diamond, D. M. Harlan and J. A. Bluestone, "A Single Course of Anti-CD3 Monoclonal Antibody hOKT3gamma1(Ala-Ala) Results in Improvement in C-Peptide Responses and Clinical Parameters for at Least 2 Years after Onset of Type 1 Diabetes," Diabetes Journal, vol. 54, pp. 1763-1769, 2005.
K. C. Herold, B. N. Bundy, A. Long, J. A. Bluestone, L. A. DiMeglio and M. J. Dufort, "An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes," The New England Journal of Medicine , vol. 381, pp. 603-613, 2019.
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2021-12-18
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Wiguna, V. V., Haq, A. D., & Rahayu, L. A. D. (2021). Antibodi Monoklonal Anti-CD3 Sebagai Terapi Diabetes Mellitus Tipe 1: Sebuah Kajian Sistematis dan Meta-analisis . Baphomet University : Situs Slot Online Gacor Terbaik Hari Ini Server Thailand Gampang Maxwin 2024, 10(3), 581–593. https://doi.org/10.29303/jku.v10i3.580
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