An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease.

Autor: Kazi ZB; Division of Medical Genetics, Department of Pediatrics, Duke University Health System, Durham, NC, USA., Desai AK; Division of Medical Genetics, Department of Pediatrics, Duke University Health System, Durham, NC, USA., Troxler RB; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA., Kronn D; Department of Pediatrics, New York Medical College, Valhalla, NY, USA., Packman S; Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, CA, USA., Sabbadini M; Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, CA, USA., Rizzo WB; Department of Pediatrics, University of Nebraska Medical Center, Nebraska Medical Center Omaha, Omaha, NE, USA., Scherer K; Department of Neurology, University of Arizona, Tucson, AZ, USA., Abdul-Rahman O; Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA., Tanpaiboon P; Quest Diagnostics and Children's National Health System, Washington, DC, USA., Nampoothiri S; Amrita Institute of Medical Sciences & Research Centre, Kochi, Kerala, India., Gupta N; All India Institute of Medical Sciences, New Delhi, India., Feigenbaum A; University of California, San Diego, CA, USA., Niyazov DM; Department of Pediatrics, Ochsner Health System, New Orleans, LA, USA., Sherry L; Department of Pediatrics, Ochsner Health System, New Orleans, LA, USA., Segel R; Medical Genetics Institute, Shaare Zedek Medical Center and the Hebrew University School of Medicine, Jerusalem, Israel., McVie-Wylie A; Sanofi Genzyme, Framingham, MA, USA., Sung C; Sanofi Genzyme, Framingham, MA, USA., Joseph AM; Sanofi Genzyme, Framingham, MA, USA., Richards S; Sanofi Genzyme, Framingham, MA, USA., Kishnani PS; Division of Medical Genetics, Department of Pediatrics, Duke University Health System, Durham, NC, USA. priya.kishnani@duke.edu.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2019 Apr; Vol. 21 (4), pp. 887-895. Date of Electronic Publication: 2018 Sep 14.
DOI: 10.1038/s41436-018-0270-7
Abstrakt: Purpose: To investigate immune tolerance induction with transient low-dose methotrexate (TLD-MTX) initiated with recombinant human acid α-glucosidase (rhGAA), in treatment-naïve cross-reactive immunologic material (CRIM)-positive infantile-onset Pompe disease (IOPD) patients.
Methods: Newly diagnosed IOPD patients received subcutaneous or oral 0.4 mg/kg TLD-MTX for 3 cycles (3 doses/cycle) with the first 3 rhGAA infusions. Anti-rhGAA IgG titers, classified as high-sustained (HSAT; ≥51,200, ≥2 times after 6 months), sustained intermediate (SIT; ≥12,800 and <51,200 within 12 months), or low (LT; ≤6400 within 12 months), were compared with those of 37 CRIM-positive IOPD historic comparators receiving rhGAA alone.
Results: Fourteen IOPD TLD-MTX recipients at the median age of 3.8 months (range, 0.7-13.5 months) had a median last titer of 150 (range, 0-51,200) at median rhGAA duration ~83 weeks (range, 36-122 weeks). One IOPD patient (7.1%) developed titers in the SIT range and one patient (7.1%) developed titers in the HSAT range. Twelve of the 14 patients (85.7%) that received TLD-MTX remained LT, versus 5/37 HSAT (peak 51,200-409,600), 7/37 SIT (12,800-51,000), and 23/37 LT (200-12,800) among comparators.
Conclusion: Results of TLD-MTX coinitiated with rhGAA are encouraging and merit a larger longitudinal study.
Databáze: MEDLINE
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