Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children With Cerebral Palsy.
Matthew J McLaughlin, Yang He, Janice Brunstrom-Hernandez and 8 others
PMID 28867665WHAT IT FOUND
A rare ABCC9 variant was associated with faster weight-adjusted baclofen clearance in 49 children with cerebral palsy, but not unadjusted clearance.
Response findings were limited by tiny carrier numbers, so this is not a dosing guide.
Key findings
01In 49 children with clearance data, the ABCC9 rs11046232 AT genotype remained significantly associated with higher weight-corrected baclofen clearance after multiple-testing correction (0.51 ± 0.05 vs 0.25 ± 0.07 L/hr/kg, adjusted p<.001).
02No statistically significant associations were observed for uncorrected apparent oral baclofen clearance after multiple-testing adjustment.
03Significant clinical response associations appeared only when improvement was measured as mean MTS R1 hamstring angle without an electronic device; ABCC12 rs16945874 CA carriers (n=7) had greater mean MTS R1 relative than CC homozygotes (36.4 ± 18.4 vs 4.4 ± 11.6, adjusted p=0.01).
STILL TO COME
How it was doneWhat they foundWhat it means for PTs
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What it does not show
The study was exploratory and small: only 49 children had clearance data, and only 36 had hamstring measurements. The main clearance association rested on only 3 children with the rare ABCC9 variant, so it could not be confirmed. Many nominal genetic associations lost significance after correcting for the large number of tests. Clinical response data were limited, and the significant response finding depended on using a non-electronic goniometer measurement. The study did not test whether genotype-guided baclofen dosing improves spasticity or reduces adverse effects. The relevance of ABCC9 and response variants to baclofen transport or clinical effect is unknown.
Declared interests
The authors reported no financial disclosures and no conflicts of interest. The publication types list NIH extramural research support.
The easy way to misread this
Do not read this as evidence that baclofen works or that ABCC9 genotype should guide dosing. The clearance association came from only 3 children with the rare variant, and the response associations were exploratory, depended on how hamstring angle was measured, and need validation.