The addition of anifrolumab to usual lupus treatment has been shown to improve disease activity and reduce glucocorticoid use in adult patients with moderate to severely active SLE.
The phase 3 TULIP-2 trial assessed the effect of the monoclonal antibody- which inhibits signalling through the type I interferon receptor – in 362 patients from 16 countries, including Australia.
Led by Professor Eric Morand from the Centre for Inflammatory Disease at Monash University, the study found monthly IV anifrolumab for 48 weeks resulted in a statistically significant improvement in the British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response at 1-year compared to placebo (47.8% v 31.5%; p=0.001).
The BICLA response rates were 48% versus 30.7% in the subgroup of patients with a high interferon gene signature and 46.7% v 35.5% in those with a low interferon gene signature.
The study found 80.7% of patients in the trial were taking glucocorticoids at baseline.
Among those receiving ≥10 mg daily prednisone or equivalent at baseline, there was a sustained reduction to ≤7.5 mg in 51.5% of the patients receiving anifrolumab and in 30.2% receiving placebo (adjusted P=0.01).
As well, almost half (49%) of patients with at least moderately active skin disease had a 50% or more reduction in their Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI).
However there was no demonstrated benefit from treatment in other secondary endpoints such as swollen and tender joint counts or annualised flare rate.
The study found the most frequent adverse events with the monoclonal antibody were upper respiratory tract infections, nasopharyngitis, infusion-related reactions, bronchitis and herpes zoster.
Cutaneous herpes zoster occurred in 7.2% of treated patients compared to 1.1% of controls.
However serious adverse events were less frequent in the anifrolumab-treated group than the placebo group (8.3% v 17%), as were discontinuation rates (2.8% v 7.1%).
The study noted that in the earlier TULIP-1 trial, anifrolumab did not show a significant effect on the primary endpoint using the Systemic Lupus Erythematosus Responder Index (SRI).
“The BICLA is based on BILAG-2004, which can register both partial and complete improvement within an organ system. In contrast, the SRI (the primary end point in the first phase 3 trial, a SLEDAI-based measure) requires complete resolution within a particular item to register change and cannot capture partial improvements,” they said.
An accompanying Editorial in the NEJM said that as lupus was clinically very heterogeneous and manifest in multiple organ systems, response to treatment was difficult to capture without the use of complex end-point measures.
It noted the drug had now shown benefit over placebo in five of six primary and key secondary endpoints across three trials (MUSE, TULIP-1 and TULIP 2).
“Given the need to bring drugs to patients with SLE, the lupus community has urged regulators to consider trial designs that allow greater flexibility in defining success. For example, perhaps a benefit with respect to just one of two end points — the SRI or the BCLA — needs to be observed to declare a drug effective in this complex disease,” it said.
It noted that blockade of type I interferon receptor signalling has been considered a compelling target to correct immune dysregulation in SLE.
“Activation of the receptor has been shown to be a central pathogenic mediator of SLE on the basis of microarray analysis of gene expression of peripheral-blood cells, which show overexpression of hundreds of gene transcripts induced by type I interferon, collectively known as the type I interferon gene signature.”