Prospective, systematically recorded mycophenolate safety data in Graves' orbitopathy

J Endocrinol Invest. 2016 Jun;39(6):687-94. doi: 10.1007/s40618-016-0441-9. Epub 2016 Feb 17.

Abstract

Context: The antiproliferative mechanism of mycophenolate acid (MPA) suggests a beneficial effect in patients with Graves' orbitopathy (GO).

Objective: To systematically analyze for the first time adverse events (AEs) during MPA treatment in GO.

Design: Prospective longitudinal study.

Setting: Academic tertiary referral center with a joint thyroid-eye clinic.

Patients: Fifty-three consecutive, unselected patients with clinically active and moderate-to-severe GO.

Methods: MPA 0.720 g was given once daily for 24-weeks in GO patients. AEs were documented and coded according to the standardized medical dictionary for regulatory activities (MedDRA). AE were followed up and seriousness as defined by ICH-guideline E6 was documented. All AEs were analyzed regarding a possible underlying cause and if not, graded as side effect (SE).

Results: Fifty GO patients (93 %) had Graves' disease, 37 (70 %) and 29 (54.7 %) were female and smoker, respectively. Thirty-six patients (68 %) reported at least one AE. A total of 88 AEs were documented, most frequent AEs were insomnia (N = 6), fatigue (N = 5) and optic neuropathy (N = 5), while other AEs occurred in up to three patients (5.6 %), only. In 12 (23 %) patients, at least one SE occurred. All 17 reported SE, i.e. mild infections and gastrointestinal intolerance were within the known safety profile of MPA. No patient dropped MPA medication because of drug-induced SE. Most AEs showed a recovered (76 %) or recovering (16 %) outcome. Seven (13 %) patients were hospitalized, five (62 %) due to optic neuropathy, none of these events was graded as SE.

Conclusions: MedDRA-coded data documented the good tolerance of a moderate MPA dose in GO patients.

Keywords: Graves’ orbitopathy; ICH guideline; Medical dictionary for regulatory activities (MedDRA); Mycophenolate; Safety.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / therapeutic use*
  • Female
  • Graves Ophthalmopathy / drug therapy*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Patient Safety
  • Prospective Studies
  • Tertiary Care Centers
  • Young Adult

Substances

  • Antibiotics, Antineoplastic
  • Mycophenolic Acid