Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations.
BACKGROUND
Orbital morphological changes are often present in patients with Graves' disease (GD) already at diagnosis, and cyclooxygenase type 2 (COX-2) is overexpressed in active Graves' ophthalmopathy (GO).


OBJECTIVE
To investigate if adjuvant treatment of GD with the COX inhibitor and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist diclofenac decreases the development of ophthalmopathy and if laboratory parameters are affected.


METHODS
This is a multicenter trial where 61 subjects were randomized to methimazole (block and replace with l-thyroxine) either with or without diclofenac 50 mg 1 × 2 for 12 months. The primary end point development of GO after 24 months was evaluated. Smoking habits were registered and the thyroid parameters TSH, free T4, free T3, TSH receptor antibodies (TRAb) and anti-TPO were followed. Safety parameters (kidney, liver and blood) and adverse events were regularly registered.


RESULTS
GO developed in 11% (n = 3) of the patients treated with diclofenac and in 21% (n = 6) of the controls (p = 0.273). The adverse event profile was acceptable without any severe events related to diclofenac. Both TRAb and anti-TPO concentrations decreased during treatment with methimazole, but the anti-TPO concentrations were lower in patients treated with diclofenac after 15 months (p = 0.031). The TRAb concentrations were not significantly changed between groups. Smokers had higher concentrations of TRAb than nonsmokers both at diagnosis of GD (p = 0.048) and after 15 months (p = 0.042).


CONCLUSIONS
Treatment with diclofenac had no significant influence on development of GO. Diclofenac reduces anti-TPO concentrations and seems to be safe to use in GD patients.
Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
Mikael
M
Lantz
Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden.
Jan
J
Calissendorff
Department of Clinical Neurosciences, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Frank
F
Träisk
Department of Clinical Neurosciences, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Leif
L
Tallstedt
Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
Tereza
T
Planck
Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden.
Ove
O
Törring
Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
Bengt
B
Hallengren
Department of Endocrinology and Ophthalmology, Skåne University Hospital Malmö, Malmö, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
Peter
P
Åsman
Anti-TPO; Diclofenac; Smoking; TSH receptor antibodies