### Abstract

Background: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. Methods: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. Results: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1–28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1–8) for methotrexate, (2–6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4–28) for tocilizumab. Conclusion: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.

Original language | English (US) |
---|---|

Journal | Seminars in Arthritis and Rheumatism |

DOIs | |

State | Accepted/In press - Jan 1 2018 |

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### Keywords

- Fragility index
- Giant cell arteritis
- Meta-analysis
- Randomized control trials
- Tocilizumab

### ASJC Scopus subject areas

- Rheumatology
- Anesthesiology and Pain Medicine

### Cite this

*Seminars in Arthritis and Rheumatism*. https://doi.org/10.1016/j.semarthrit.2017.12.009

**Treatments for giant cell arteritis : Meta-analysis and assessment of estimates reliability using the fragility index.** / Berti, Alvise; Cornec, Divi; Medina Inojosa, Jose R.; Matteson, Eric Lawrence; Murad, Mohammad H.

Research output: Contribution to journal › Article

}

TY - JOUR

T1 - Treatments for giant cell arteritis

T2 - Meta-analysis and assessment of estimates reliability using the fragility index

AU - Berti, Alvise

AU - Cornec, Divi

AU - Medina Inojosa, Jose R.

AU - Matteson, Eric Lawrence

AU - Murad, Mohammad H

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. Methods: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. Results: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1–28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1–8) for methotrexate, (2–6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4–28) for tocilizumab. Conclusion: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.

AB - Background: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. Methods: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. Results: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1–28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1–8) for methotrexate, (2–6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4–28) for tocilizumab. Conclusion: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.

KW - Fragility index

KW - Giant cell arteritis

KW - Meta-analysis

KW - Randomized control trials

KW - Tocilizumab

UR - http://www.scopus.com/inward/record.url?scp=85042510457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042510457&partnerID=8YFLogxK

U2 - 10.1016/j.semarthrit.2017.12.009

DO - 10.1016/j.semarthrit.2017.12.009

M3 - Article

JO - Seminars in Arthritis and Rheumatism

JF - Seminars in Arthritis and Rheumatism

SN - 0049-0172

ER -