SAN FRANCISCO – Mounting evidence supports the use of tocilizumab in giant cell arteritis (GCA), and a new study supports use of the drug for induction and maintenance therapy in patients with newly diagnosed or relapsed GCA in the context of rapidly tapered glucocorticoid therapy.
“This is the first randomized controlled trial to prove efficacy of tocilizumab in induction and maintenance of remission in GCA. Tocilizumab reached the primary and secondary endpoints in our trial compared with placebo. After 12 months of therapy, more serious adverse events were observed in the placebo group,” said lead author Dr. Sabine Adler, University Hospital, Bern, Switzerland. Dr. Adler presented results of this late-breaking abstract at a special session during the annual meeting of the American College of Rheumatology.
Dr. Sabine Adler
A recent small open-label trial showed that tocilizumab was effective in patients with refractory GCA and unacceptable side effects on glucocorticoid (GC) therapy (Sem Arthr Rheum. Dec. 26, 2014. DOI:10.1016/j.semarthrit.2014.12.005). The present study was of newly diagnosed patients or those who had relapsed.
GCA is characterized by destructive inflammation in the walls of medium and large arteries. GC treatment has been the mainstay of therapy, controlling symptoms and reducing the risk of dreaded complications such as blindness, stroke, and claudication. But many patients require prolonged treatment, and cumulative doses of GC lead to substantial toxicity and morbidity. Thus, a better treatment is needed.
IL-6, the target of tocilizumab, is one of the cytokines involved in the pathogenesis of GCA. It is elevated in the serum and tissue of affected patients, Dr. Adler explained.
Dr. Adler and colleagues conducted a single-center, randomized, placebo-controlled trial evaluating tocilizumab in 30 patients with newly diagnosed or recurrent GCA. Patients were randomized in a 2:1 ratio to receive tocilizumab 8 mg/kg IV plus oral GC or IV placebo and oral GC. Infusions were given every 4 weeks for 1 year, over which time GC dose was slowly tapered to 0 mg in all patients. Some patients underwent angiography to rule out or define aortic involvement. Most patients in the trial had new onset GCA, she said.
The primary endpoint was complete remission at week 12 with GC dose of 0.1 mg/kg/day. Complete remission was defined as the absence of clinical signs and symptoms of GCA plus negative values for C-reactive protein (CRP) and erythrocyte sedimentation rate. At 12 weeks, the complete response rate was 85% for tocilizumab versus 40% for placebo, a significant difference. At the end of the trial, 85% and 20%, respectively, had not had a relapse; this difference was significant.
Placebo patients received a higher cumulative dose of GC, she continued.
There were 7 serious adverse events reported in the tocilizumab arm and 5 in the placebo arm; 1 death occurred in the placebo arm due to myocardial infarction.
“A closer look at serious adverse events reveals few cardiovascular problems,” Dr. Adler continued. Back pain and psychosis were reported as reasons for hospitalization.
During the question and answer session, an audience member noted that it was difficult to understand how a short-term treatment is effective in a chronic disease. “Probably patients will relapse when they stop the medication, so we are not on the ‘green’ side yet,” she replied. Dr. Adler noted that it could be possible that a reduced dose of tocilizumab could be effective but have fewer side effects, but that has not been studied.
Tocilizumab was provided by Roche for this investigator-initiated trial. Dr. Adler reported no financial disclosures.