Reverse transcriptase inhibitors in Aicardi-Goutières syndrome: A crossover clinical trial.
Yanick J Crow, Tracy A Briggs, Despina Eleftheriou and 5 others
PMID 39630935WHAT IT FOUND
Reverse transcriptase inhibitors did not significantly lower interferon scores after 6 weeks in children with Aicardi-Goutières syndrome.
Single-drug arms showed no effect. Triple therapy lowered scores at 3 weeks but not 6, and the finding failed sensitivity checks. Poor adherence limited the trial.
Key findings
01Neither abacavir nor lamivudine alone significantly reduced the primary interferon score after 6 weeks.
02Triple therapy did not significantly reduce the primary interferon score at 6 weeks, and the significant 3-week finding was not mirrored by changes in interferon-alpha protein levels.
03Adherence was poor in the final treatment arm, with only four of 12 patients able to fully tolerate the prescribed dosing for 6 weeks.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The study was severely underpowered, recruiting 13 patients against a target of 24, which limits the certainty of any negative findings. Adherence was poor, particularly in the triple therapy arm, where only four of 12 patients completed the 6-week course, making it difficult to assess the true efficacy of the combined regimen. The trial was open-label and non-placebo-controlled, which introduces potential bias in outcome assessment, although the primary outcome was a laboratory measure. Two patients did not have elevated interferon scores at baseline, which may have diluted any treatment effect in the overall analysis.
Declared interests
The authors declare the absence of any conflicts of interest, financial or otherwise. The University of Edinburgh and NHS Lothian acted as joint sponsors.
The easy way to misread this
Do not interpret the significant 3-week reduction in interferon scores with triple therapy as evidence of clinical efficacy. This finding was not supported by the secondary protein measure, failed the sensitivity analysis for missing data, and occurred in a trial that was underpowered and had poor adherence.