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Cochrane Database of Systematic Reviews

Tratamiento con yodo radioactivo versus fármacos antitiroideos para la enfermedad de Graves

Información

DOI:
https://doi.org/10.1002/14651858.CD010094.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 18 febrero 2016see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:

  1. Grupo Cochrane de Trastornos metabólicos y endocrinos

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Chao Ma

    Correspondencia a: Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Shanghai, China

    [email protected]

    [email protected]

  • Jiawei Xie

    Stomatology, Putuo Liqun Hospital, Shanghai, China

  • Hui Wang

    Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Shanghai, China

  • Jinsong Li

    Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Shanghai, China

  • Suyun Chen

    Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Shanghai, China

Contributions of authors

All review authors read and approved the final review draft.

Chao Ma (CM): protocol draft, search strategy development, data analysis, data interpretation and future review update.

Jiawei Xie (JWX): trial selection and data extraction.

Hui Wang (HW): search strategy development, trial selection, data extraction and data interpretation.

Jinsong Li (JL): trial selection, data analysis and data interpretation.

Suyun Chen (SYC): acquisition of trial copies, trial selection, data extraction, data analysis and future review update.

Sources of support

Internal sources

  • Dr. Ma was supported by National Natural Science Fund (no. 81271612), China.

External sources

  • No sources of support supplied

Declarations of interest

Chao Ma: none known.

Jiawei Xie: none known.

Hui Wang: none known.

Jinsong Li: none known.

Suyun Chen: none known.

Acknowledgements

The authors wish to acknowledge Dr. Al Driedge from the Department of Nuclear Medicine/Oncology, University of Western Ontario, London, Canada for his invaluable comments, editing and formatting. We also thank Dr. Ove Torring and Dr. Danyun Chen for providing the required data for the meta‐analysis. The search strategies were designed by Maria‐Inti Metzendorf (Trials Search Co‐ordinator of the CMED Group).

Version history

Published

Title

Stage

Authors

Version

2016 Feb 18

Radioiodine therapy versus antithyroid medications for Graves' disease

Review

Chao Ma, Jiawei Xie, Hui Wang, Jinsong Li, Suyun Chen

https://doi.org/10.1002/14651858.CD010094.pub2

2012 Sep 12

Radioiodine therapy versus anti‐thyroid medications for Graves' disease

Protocol

Chao Ma, Jiawei Xie, Hui Wang, Jinsong Li, Suyun Chen

https://doi.org/10.1002/14651858.CD010094

Differences between protocol and review

In response to the requirements of the CMED Group, we also evaluated the outcome measure development or worsening of Graves' opthalmopathy as a primary outcome.

We also planned to evaluate the effects of steroids on preventing the development and progression of Graves' opthalmopathy. However, a systematic review reported that prednisolone prophylaxis was highly effective in preventing the progression of Graves' opthalmopathy in patients with pre‐existing Graves' opthalmopathy treated by radioiodine. Therefore, we did not assess the effects of steroids on Graves' opthalmopathy in this review. Moreover, these data were not reported in the two included trials.

We did not carry out the planned subgroup analyses 'dose of radioiodine', 'age' and 'gender' because of an insufficient number of trials, no information or both.

Due to the time lag between publication of the protocol and the final review draft the whole review was completely restructured by the editorial office of the CMED Group and the newest standards were implemented.

Notes

We have based parts of the background, the methods section, appendices, additional tables and figures 1 to 3 of this review on a standard template established by the CMED Group.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included trial (blank cells indicate that the trial did not measure that particular outcome).
Figuras y tablas -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included trial (blank cells indicate that the trial did not measure that particular outcome).

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Comparison 1 Radioiodine versus methimazole, Outcome 1 Development or worsening of Graves' ophthalmopathy.
Figuras y tablas -
Analysis 1.1

Comparison 1 Radioiodine versus methimazole, Outcome 1 Development or worsening of Graves' ophthalmopathy.

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Comparison 1 Radioiodine versus methimazole, Outcome 2 Adverse events: hypothyroidism.
Figuras y tablas -
Analysis 1.2

Comparison 1 Radioiodine versus methimazole, Outcome 2 Adverse events: hypothyroidism.

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Comparison 1 Radioiodine versus methimazole, Outcome 3 Recurrence of hyperthyroidism (relapse).
Figuras y tablas -
Analysis 1.3

Comparison 1 Radioiodine versus methimazole, Outcome 3 Recurrence of hyperthyroidism (relapse).

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Comparison 1 Radioiodine versus methimazole, Outcome 4 Participants in euthyroid state.
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Analysis 1.4

Comparison 1 Radioiodine versus methimazole, Outcome 4 Participants in euthyroid state.

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Radioiodine therapy compared with antithyroid medications for Graves' disease

Patient: participants with Graves' disease

Settings: outpatients

Intervention: radioiodine

Comparison: methimazole

Outcomes

Assumed risk

Corresponding risk

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Methimazole

Radioiodine

Health‐related quality of life
[measured by the validated questionnaire SF‐36]

Follow‐up: 4 years and 14 to 21 years

See comment

See comment

See comment

425 (2)

See comment

2 trials assessed this outcome but no quantitative data for comparisons between intervention groups were provided; trial authors in 1 trial reported that there were no differences in the results of the SF‐36 scores between the 2 treatment groups

Development and worsening of Graves' ophthalmopathy
[examination by ophthalmologists]
Follow‐up: 2 years and 4 years

186 per 1000

361 of 1000 (260 to 502)

RR 1.94 (1.40 to 2.70)

417 (2)

⊕⊕⊝⊝
lowa

‐

Individuals in euthyroid state
[measured by serum thyroid hormone levels within the normal range]

Follow‐up: at least 4 years

See comment

See comment

See comment

112 (1)

See comment

No participant who underwent radioiodine treatment achieved an euthyroid state compared to 4/68 participants not becoming euthyroid treated by methimazole (Tallstedt 1992); however, in this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism

Recurrence of hyperthyroidism (relapse)
[measured by serum thyroid hormone levels above the normal range after withdrawal of methimazole or end of radioiodine treatment]

Follow‐up: at least 4 years

256 per 1000

51 of 1000 (3 to 680)

RR 0.20 (0.01 to 2.66)

417 (2)

⊕⊝⊝⊝
very lowb

‐

Adverse events other than development or worsening of Graves' disease

(a) Hypothyroidism [measured by TSH and/or thyroid hormones]

(b) Drug reactions

Follow‐up: (a) at least 2 years (b) at least 4 years

See comment

See comment

See comment

(a) 104 (1)

(b) 215 (2)

a) ⊕⊝⊝⊝
very lowc

b) ⊕⊝⊝⊝
very lowd

(a) 39 of 41 participants developed hypothyroidism after radioiodine treatment for Graves' disease, compared with 0 of 65 participants receiving methimazole (Tallstedt 1992); however, in this trial thyroxine was not introduced early in both treatment groups in order to avoid hypothyroidism

(b) 23 of 215 participants (11%) reported adverse effects likely related to methimazole treatment

All‐cause mortality

Follow‐up: at least 4 years and 14 to 21 years

See comment

See comment

See comment

425 (2)

See comment

No quantitative data for all‐cause mortality were reported

Socioeconomic effects
[costs per patient, based on the official hospital reimbursement system in Sweden]

Follow‐up: 2 years

See comment

See comment

See comment

112 (1)

See comment

Costs for patients without relapse and methimazole treatment were USD 1126/USD 1164 (young/older methimazole group) and for radioiodine treatment USD 1862

Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio; SF‐36: 36‐item Short Form Health Status Survey; TSH: thyroid‐stimulating hormone

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Assumed risk was derived from the event rates in the comparator groups.
aDowngraded by two levels: one level because of performance and detection bias and one level because of imprecision (see Appendix 12).
bDowngraded by three levels: two levels because of serious inconsistency and one level because of imprecision (see Appendix 12).
cDowngraded by three levels: one level because of indirectness and two levels because of imprecision (see Appendix 12).
cDowngraded by three levels: one level because of risk of bias, one level because of indirectness and one level because of imprecision (see Appendix 12).

Figuras y tablas -
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Table 1. Overview of study populations

Intervention(s) and
comparator(s)

Sample sizea

Screened/eligible
[N]

Randomised
[N]

ITT
[N]

Analysed
[N]

Finishing trial
[N]

Randomised finishing trial
[%]

Follow‐up
(extended follow‐up)b

Traisk 2009

Radioiodine

Primary endpoint was the difference in the proportion of participants with worsening or development of thyroid‐associated ophthalmopathy during a 4‐year follow‐up in the 2 groups (intention‐to‐treat analysis). A comparison (0.05, two‐tailed test) of the binomial proportions between 2 groups of 300 patients each would give more than 90% probability (power) to detect a true difference of 10%

482/333

‐

163

163

163

‐

24 months (4 years)

Methimazole

‐

150

150

150

‐

total:

333

313

313

313

94

Tallstedt 1992e

Radioiodine

‐

179

41

‐

39f

39

95

At least 24 months (at least 48 months; 3 years; 5 years; 14‐21 years)g

Methimazole

71

65f

64

90

total:

112

104

103

92

Grand total

All radioiodine‐treated participants

204

All participants treated with methimazole

221

All interventions

425

"‐" denotes not reported
aInformation about power calculation, sample size etc. in trial publication or report.
bFollow‐up under randomised conditions until end of trial or, if not available, duration of intervention; extended follow‐up refers to follow‐up of participants once the original study was terminated as specified in the power calculation.
cEnrollment in the study started in May 1996. By the second half of 2002, it was obvious that the inclusion rate was too slow to obtain the full number of participants within a reasonable period of time and the study was closed in 2003. This meant that with the above specifications and the number of observations obtained so far (333 enrolled participants), the study had a power of about 70%. With the 4‐year clinical follow‐up, the study was terminated by the end of 2007.
dThe cumulative drop‐out (last observation carried forward) from the ophthalmological follow‐up in the radioiodine group and the medical treatment group, respectively, was as follows: at 1 year, 3% and 1%; at 2 years, 6% and 3%; and at 3 years, 10% and 9%, respectively. At 4 years (i.e. after protocol for ophthalmological follow‐up), 20% of the participants in both groups were still followed by ophthalmologists.
eParticipants were stratified into two age groups (20 to 34 years (group 1) and 35 to 55 years (group 2)). Participants in group 1 were randomised to treatment with methimazole for 18 months or subtotal thyroidectomy, participants in group 2 to methimazole, subtotal thyroidectomy or radioiodine treatment. Numbers in the table reflect the participants being treated with methimazole or radioiodine.
fWith regard to occurrence of ophthalmopathy within two years after the initiation of therapy.
gDifferent follow‐up times according to various publications of extended follow‐up.

ITT: intention‐to‐treat
Figuras y tablas -
Table 1. Overview of study populations
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Comparison 1. Radioiodine versus methimazole

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Development or worsening of Graves' ophthalmopathy Show forest plot

2

417

Risk Ratio (M‐H, Random, 95% CI)

1.94 [1.40, 2.70]

2 Adverse events: hypothyroidism Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

3 Recurrence of hyperthyroidism (relapse) Show forest plot

2

417

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 2.66]

4 Participants in euthyroid state Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 1. Radioiodine versus methimazole
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