Aussie connection to new steroid-sparing option as tocilizumab shortages continue.
An international multi-centre trial with Australian sites has found that mavrilimumab was more effective than placebo in reducing flares and maintaining sustained remission in patients with giant cell arteritis (GCA).
With few treatment options currently available for GCA, there’s a pressing need for more. Patients with GCA are often treated with glucocorticoids, with associated high relapse rates and toxicity. Using tocilizumab in combination with glucocorticoids can spare steroids, but around one-quarter to one-third of patients don’t achieve sustained remission, and adverse events can result in discontinuation.
Apart from current shortages, a further issue with tocilizumab is that it masks patient blood levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are useful indicators of disease activity.
Mavrilimumab inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), which is implicated in the pathogenesis of GCA. It has demonstrated efficacy in phase 2 studies of rheumatoid arthritis, and also showed early promise for treating covid, although the phase 3 trial failed to achieve the primary endpoint.
Seventy patients in the phase 2, randomised double-blind study were allocated to receive either 150mg mavrilimumab or placebo injections every two weeks, in conjunction with a 26-week prednisone taper. The authors noted that in previous studies of steroid tapers most disease flares occur within the first 6 months, and thus limited the trial to expedite results – although there was a further 12-week observation period.
The primary endpoint was time to first GCA flare up to week 26, and secondary endpoint was sustained remission at week 26. Safety was assessed through to week 38. The study, funded by Kiniksa Pharmaceuticals, was published in Annals of the Rheumatic Diseases.
Of the 42 patients taking mavrilimumab, eight (19%) experienced a flare, compared with 13 of 28 (46%) taking the placebo (HR 0.38, p=0.026). More than 80% of the mavrilimumab group achieved sustained remission at week 26, compared with 50% of the placebo group, a statistically significant difference. The mean cumulative dose of prednisone was lower by week 26 for mavrilimumab patients, although the difference was not statistically significant.
Adverse events were reported by most patients in both groups, with non-specific headache, nasopharyngitis and neck pain the most frequently reported in the mavrilimumab group.
“This trial provides the first evidence of the efficacy and safety of mavrilimumab in patients with GCA,” wrote the authors.
“Mavrilimumab with a 26-week prednisone taper was superior to placebo with a 26-week prednisone taper in reducing the risk of flare and maintaining sustained remission,” they said adding that it was well tolerated, and the overall incidence of adverse events and serious adverse events was similar between groups.
This work comes on the back of increasing calls for more options in GCA, with ongoing shortages of tocilizumab highlighting the dearth of available therapies. This week in a communication to Australian prescribers, Roche confirmed that while shortages continue, supplies have begun to improve and are available for a broader cohort of patients. The TGA has extended the Serious Scarcity Substitution Instrument (SSSI) to 30 April 2022.
Speaking to Rheumatology Republic about the trial before the results were published, co-author Professor Ian Wicks, of the Walter and Eliza Hall Institute of Medical Research, said there is still an approvals process to go through and it could be a few years before clinicians are able to access the treatment for their patients.
