Anti-tumour necrosis factor treatment with infliximab in a case of giant cell arteritis resistant to steroid and immunosuppressive drugs

P. Airò, C. M. Antonioli, M. Vianelli and P. Toniati

Clinical Immunology, Spedali Civili, Brescia, Italy

SIR, The therapeutic approach to giant cell arteritis (GCA) remains based on the long-term use of high doses of corticosteroids. No real alternative exists in cases in which the disease is not controlled or recurs despite appropriate therapy with steroids, or in which unacceptable side-effects arise. Although small studies have suggested that immunosuppressive drugs, such as azathioprine and methotrexate, could be used as steroid-sparing agents [13], there is no conclusive evidence for this.

A potential advantage of anti-tumour necrosis factor (TNF) treatment is suggested by the histological features showing mononuclear infiltration consisting of activated macrophages and Th1 T-lymphocytes [4]. Moreover, although an increased serum concentration of TNF-{alpha} has not been observed in patients with GCA [5, 6], it has been reported that this may correlate with the intensity of the systemic inflammatory response [7].

Finally, GCA is associated with different TNF microsatellite polymorphisms [8] and with the HLA-DRB1 shared epitope [9], found also in the majority of patients with rheumatoid arthritis, in whom anti-TNF treatment has been proved to have clear efficacy.

We report here the case of a 75-yr-old woman with a form of GCA that was persistently active despite prolonged treatment with steroids and immunosuppressive drugs, who benefited from anti-TNF treatment with infliximab.

The patient was first evaluated elsewhere in June 1996. Because of the presence of shoulder girdle pain and stiffness, low-grade fever and weight loss, polymyalgia rheumatica (PMR) was diagnosed, after an occult neoplasm had been excluded. Although the patient had received 6 months of treatment with prednisone 15 mg/day, when we evaluated her in December 1996, she complained of jaw claudication and temporoparietal headache. No signs of peripheral arthro- or tenosynovitis were observed. The erythrocyte sedimentation rate was 120 mm/1st h and the C-reactive protein concentration 52 mg/l. Rheumatoid factor and antinuclear antibodies were negative. X-rays of the hands did not show relevant abnormalities. Although we did not observe tenderness or thickness of the temporal arteries, a biopsy was performed. This did not show signs of active or healed arteritis. However, it is known that the chance of finding a positive biopsy is very low in patients who have received prolonged therapy with steroids [10]. A diagnosis of GCA was nevertheless made, because of the presence of typical symptoms and according to the ARA classification criteria [11]. Treatment with prednisone 50 mg/day was started.

An incomplete response was observed, with prolonged persistence of typical headache and girdle symptoms and permanence of elevated levels of acute-phase reactants. The lack of response to high doses of steroids ruled out definitively the hypothesis of PMR without arteritis. Moreover, the patient suffered from multiple osteoporotic vertebral fractures. For these reasons, azathioprine 100 mg/day was added to the steroid treatment from February 1997 to April 1999. Since then, because of the lack of benefit, this drug was replaced by methotrexate 10 mg/week. Despite a reduction in headache, the disease was not controlled and the steroid dose was never reduced below 20 mg/day. The doses of immunosuppressives used in our patient were similar to those used in studies reporting their possible utility in the treatment of GCA [13].

On the basis of these considerations, in January 2001, after having obtained the patient's informed consent, infliximab 3 mg/kg was added to the treatment with steroid plus methotrexate, and was repeated at weeks 2, 6, 14, 22. As shown in Table 1Go, a progressive improvement was observed, with marked decreases in symptoms and acute-phase markers, and an improvement in functional status. This was assessed by the Health Assessment Questionnaire, which has been demonstrated to be useful for this purpose in patients with PMR [12].


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TABLE 1.  Patient evolution after treatment with infliximab

 
Although the present report describes only one case, the outcome suggests that anti-TNF therapy might offer a new approach to the treatment of GCA resistant to steroid and immunosuppressive drugs, and that controlled studies might be warranted to formally address this issue.

Notes

Correspondence to: P. Airò, Servizio di Immunologia Clinica, Spedali Civili, 25123 Brescia, Italy. Back

References

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Accepted 7 August 2001