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Treatment options for giant cell arteritis (GCA) are limited. Glucocorticoids are the mainstay of therapy, but relapses are common and often necessitate high cumulative doses of glucocorticoids.1,–,4 Interleukin 6 (IL-6) might be a key mediator of vascular inflammation in patients with GCA. Temporal artery biopsy samples show enhanced IL-6 production,5 and IL-6 levels generally correlate with disease activity.6 This prompted us to investigate the effects of anti-IL-6 receptor therapy with tocilizumab in three patients with refractory GCA.
Our first patient (79-year-old male) suffered from fever, night sweats and weight loss. Inflammation markers were elevated (C reactive protein (CRP) 168 mg/l), temporal artery biopsy showed typical histological signs and positron emission tomography (PET)/CT scans demonstrated large-vessel vasculitis (figure 1). Despite excellent initial response, we could not taper prednisone to doses less than 30 mg/day. Since methotrexate was contraindicated (chronic renal failure), we added azathioprine without clinical improvement.
Our second patient (72-year-old female) presented with unilateral anterior uveitis and subungual haemorrhages initially suggesting small-vessel vasculitis. She also suffered from weight loss, night sweats and loss of appetite. Systemic inflammation markers were elevated (CRP 307 mg/l). After extensive diagnostic workup, we diagnosed undifferentiated vasculitis. Again, we could not taper prednisone below 30 mg/day, even after adding mycophenolate mofetil (methotrexate was contraindicated; azathioprine was not tolerated). After 4 months, the patient still had systemic inflammation (CRP 53 mg/l) and complained of headaches and visual disturbances. We performed a PET/CT scan and found widespread involvement of the aorta, subclavian and carotid arteries (figure 1). Despite a negative temporal artery biopsy, we considered GCA as the most likely diagnosis.
Our third patient (71-year-old female) was diagnosed with GCA on the basis of new-onset headaches, diplopia, systemic symptoms and elevated CRP levels. When the patient was tapered below 30 mg of prednisone, night sweats, loss of appetite and headaches recurred and CRP levels rose again. At that time, we found subclavian artery involvement in magnetic resonance angiography and thickening of femoral artery vessel walls with halo sign indicative of vasculitis. The patient did not tolerate methotrexate due to gastrointestinal side effects.
In all three patients, we started tocilizumab (8 mg/kg bodyweight) infusions every 4 weeks for 6 months. Only in our third patient, there was delay between the first and second infusion because of osteoporotic fractures during rehabilitation. We report 6-month follow-up for all patients. All patients tolerated tocilizumab well and showed a rapid clinical response with normalisation of symptoms and inflammation markers (CRP, serum amyloid A). In addition, the first two patients with positive PET/CT scans showed no metabolic activity in the follow-up scans at the end of the induction therapy (figure 1). Glucocorticoids could be tapered rapidly and safely during the induction phase. After induction therapy with tocilizumab, all patients were on prednisone doses below 7.5 mg/day (figure 2).
Despite our encouraging results, there remain uncertainties: (1) our patients might represent a subgroup of GCA patients with high systemic inflammatory response and involvement of the aorta and its main branches, showing Takayasu-like features.7 All of our three patients, however, fulfilled the American College of Rheumatology criteria for GCA.8 In contrast to the excellent response to anti-IL-6 therapy in these patients, tocilizumab might be less effective for ‘classical’ GCA patients with limited cranial involvement; (2) IL-6 shows angiogenic activity and might have positive effects on neovascularisation to compensate for vessel occlusion in GCA9; (3) suppressing the acute phase response with the general feeling of sickness may mask persistent vascular inflammation. Nonetheless, the rapid clinical and serological response to tocilizumab treatment in our patients is stimulating. Prior to routine clinical use, however, randomised controlled trials should establish the efficacy of anti-IL-6 receptor treatment in GCA.
Competing interests JZ, GS, CB, JHD and BM have received speaker's fees and travel grants from Roche.
Provenance and peer review Not commissioned; externally peer reviewed.