A systematic review and network meta-analysis comparing azacitidine and decitabine for the treatment of myelodysplastic syndrome 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1117 Public Health and Health Services

Jehad Almasri, Hassan B. Alkhateeb, Belal Firwana, Mohamad Bassam Sonbol, Moussab Damlaj, Zhen Wang, Mohammad H Murad, Aref Al-Kali

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Background: Hypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS. Methods: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence). Results: Only four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74-0.94, I 2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77-1.00, I 2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01-0.86, very low-certainty evidence). Conclusions: Azacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

Original languageEnglish (US)
Article number144
JournalSystematic Reviews
Volume7
Issue number1
DOIs
StatePublished - Sep 19 2018

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decitabine
Azacitidine
Myelodysplastic Syndromes
Health Services
Public Health
Health
Mortality
Therapeutics
Drug Costs
Patient Preference
MEDLINE
Network Meta-Analysis
Consensus
Leukemia
Hospitalization
Language
Quality of Life
Clinical Trials
Databases

Keywords

  • Azacitidine
  • Decitabine
  • Myelodysplastic syndromes
  • Network meta-analysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

A systematic review and network meta-analysis comparing azacitidine and decitabine for the treatment of myelodysplastic syndrome 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1117 Public Health and Health Services. / Almasri, Jehad; Alkhateeb, Hassan B.; Firwana, Belal; Sonbol, Mohamad Bassam; Damlaj, Moussab; Wang, Zhen; Murad, Mohammad H; Al-Kali, Aref.

In: Systematic Reviews, Vol. 7, No. 1, 144, 19.09.2018.

Research output: Contribution to journalReview article

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abstract = "Background: Hypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS. Methods: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence). Results: Only four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95{\%} CI 0.74-0.94, I 2 = 89{\%}) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95{\%} CI 0.77-1.00, I 2 = 53{\%}). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95{\%} CI = 0.01-0.86, very low-certainty evidence). Conclusions: Azacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.",
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AU - Almasri, Jehad

AU - Alkhateeb, Hassan B.

AU - Firwana, Belal

AU - Sonbol, Mohamad Bassam

AU - Damlaj, Moussab

AU - Wang, Zhen

AU - Murad, Mohammad H

AU - Al-Kali, Aref

PY - 2018/9/19

Y1 - 2018/9/19

N2 - Background: Hypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS. Methods: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence). Results: Only four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74-0.94, I 2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77-1.00, I 2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01-0.86, very low-certainty evidence). Conclusions: Azacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

AB - Background: Hypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS. Methods: We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence). Results: Only four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74-0.94, I 2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77-1.00, I 2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01-0.86, very low-certainty evidence). Conclusions: Azacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

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KW - Decitabine

KW - Myelodysplastic syndromes

KW - Network meta-analysis

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