Beneficial Effect of Pentoxifylline on Thyroid Associated Ophthalmopathy (TAO)*: a pilot study

Abstract

We have previously found that pentoxifylline (Ptx) inhibited cytokine induced HLA-DR expression and glycosaminoglycan (GAG) synthesis by retroorbital fibroblasts. We have now tested the clinical efficacy of Ptx in treating TAO. Ten patients with moderately severe ophthalmopathy were selected for study. All patients were euthyroid before and during the 12 weeks of the Ptx therapy. Serum GAG, TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies were determined sequentially. At the end of 12 weeks eight of the ten patients showed improvement in soft tissue but not in proptosis or extraocular muscle involvement. At baseline the levels of GAG (5.2±0.92 mg/dl v.s. 0.7±0.14 mg/dl, p<0.001) and TNF-alpha (33.6±6.6 pg/ml v.s. 5.4±1.3 pg/ml, p<0.001) were increased in patients compared to controls. They gradually decreased in the eight patients who responded to Ptx: after 4, 8 and 12 weeks of therapy serum GAG was 3.4±0.42 mg/dl, 2.5±0.77 mg/dl (p<0.01) and 1.1±0.2 mg/dl (p<0.001), respectively and serum TNF-alpha was 20.9±4.8 pg/ml, 14.9±2.2 pg/ml (p<0.05) and9.7±1.8 pg/ml (p<0.01), respectively. Serum GAG and TNF alpha did not fall in the two patients who did not respond. The titre of anti-eye muscle antibodies but not anti-thyroid antibodies were lower at 12 weeks. Ptx has a beneficial effect on inflammatory symptoms of TAO and associated laboratory parameters in the majority of patients.

Favorable Effect of Bromocriptine and Pentoxifylline in Mild Graves Disease Orbitopathy: A Randomized, Open, Clinical Trial

“…The particular effect of PTX in GO is the inhibition of tumor necrosis factor alpha synthesis [37]. Also, using fibroblast cell cultures and animal models, an anti-fibrotic effect has been reported [38].…”

Novel Approaches to the Management of Graves` Ophthalmopathy

“…Eight patients (80%) responded favorably in terms of an overall evaluation carried out by assesing variations of the Total Eye Score (Figure 4) 78 . Soft tissue changes and proptosis were most responsive, whereas extraocular muscle involvement response was less impressive 78 . Clearly, the results of this preliminary study must be interpreted with caution and randomized and controlled studies are, also in this case, required to assess more accurately the true effectiveness of pentoxifylline.…”

“…So far, the only available data on the effects of cytokine antagonists in vivo on GO were reported by Balazs et al using pentoxifylline 78 . This drug, an analogue of methylxanthine theobromine widely used for peripheral vascular disorders, has complex immunomodulatory effects on cytokine production 79 .…”

“…Pentoxifylline interferes with the second messenger pathways of a variety of cytokines, including TNF-á, IL-1â and transforming growth factor-â 70 . Based on this premise Balazs et al 78 , in a nonrandomized and uncontrolled study, treated 10 patients with moderately severe GO with pentoxifylline (200 mg daily iv for 10 days, followed by 1800 mg/daily orally for 4 weeks, then reduced to 1200 mg daily until the end of a 3-month treatment). Eight patients (80%) responded favorably in terms of an overall evaluation carried out by assesing variations of the Total Eye Score (Figure 4) 78 .…”

Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts

“…This agent has significant anti-cytokine activity and was shown to inhibit IL-1-, TNF-a-, and IFN-g-induced HLA-DR expression and GAG synthesis in cultural orbital fibroblasts. Ten patients with moderately severe TED were given intravenous pentoxifylline for 10 days, followed by oral therapy for an additional 10 weeks (70). Eight of the ten patients treated showed some improvement of soft tissue swelling, but not of proptosis or extra-ocular muscle involvement.…”