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Adjuvant Treatment of Graves' Disease with Diclofenac : Safety, Effects on Ophthalmopathy and Antibody Concentrations

Lantz, Mikael LU ; Calissendorff, Jan ; Träisk, Frank ; Tallstedt, Leif ; Planck, Tereza LU ; Törring, Ove ; Hallengren, Bengt LU and Åsman, Peter LU (2016) In European Thyroid Journal 5(1). p.6-50
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Thyroid Journal
volume
5
issue
1
pages
6 - 50
publisher
S. Karger AG
external identifiers
  • pmid:27099839
ISSN
2235-0640
DOI
10.1159/000443373
language
English
LU publication?
yes
id
07fe3c89-0331-47ff-afe8-f2b0700f53d4
date added to LUP
2019-06-20 08:33:59
date last changed
2019-06-24 16:30:48
@article{07fe3c89-0331-47ff-afe8-f2b0700f53d4,
  abstract     = {<p>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).</p><p>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.</p><p>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.</p><p>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).</p><p>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.</p>},
  author       = {Lantz, Mikael and Calissendorff, Jan and Träisk, Frank and Tallstedt, Leif and Planck, Tereza and Törring, Ove and Hallengren, Bengt and Åsman, Peter},
  issn         = {2235-0640},
  language     = {eng},
  number       = {1},
  pages        = {6--50},
  publisher    = {S. Karger AG},
  series       = {European Thyroid Journal},
  title        = {Adjuvant Treatment of Graves' Disease with Diclofenac : Safety, Effects on Ophthalmopathy and Antibody Concentrations},
  url          = {http://dx.doi.org/10.1159/000443373},
  doi          = {10.1159/000443373},
  volume       = {5},
  year         = {2016},
}