Anifrolumab, a human monoclonal antibody to the type I IFN receptor subunit 1, had robust efficacy in a phase 2 study in patients with active systemic lupus erythematosus ( SLE ).
The first phase 3 trial, TULIP-1, did not meet its primary endpoint, SLE responder index ( SRI ), but multiple other endpoints, including BILAG–based Composite Lupus Assessment ( BICLA ), suggested clinical benefit.
Results of the second phase 3 trial of Anifrolumab were reported.
TULIP-2 is a randomized, double-blind, placebo-controlled trial that has evaluated efficacy and safety of IV Anifrolumab 300 mg versus placebo every 4 weeks for 48 weeks in patients with moderate to severe SLE despite standard-of-care ( SOC ) treatment.
Patients met ACR SLE criteria and had SLEDAI-2K greater than or equal to 6 and BILAG more than 1 A or more than 2 B.
The primary endpoint was BICLA response at week 52.
Standard-of-care was stable except for mandatory attempts at oral corticosteroid ( OCS ) tapering to Prednisone equivalent less than or equal to 7.5 mg/d for patients receiving greater than or equal to 10 mg/d at baseline.
Of 365 randomized patients, 362 received greater than or equal to 1 dose of study drug and were included in the analyses ( Anifrolumab, n=180; placebo, n=182 ).
Baseline demographic and disease characteristics were similar between treatment groups.
Treatment completion was 85.0% for Anifrolumab and 71.4% for placebo.
Anifrolumab was superior to placebo for BICLA response (4 7.8% vs 31.5%, respectively, P=0.001 ) and key secondary endpoints: OCS reduction ( 51.5% vs 30.2%; P=0.014 ) and Cutaneous Lupus Erythematosus Disease Area and Severity Index response ( 49.0% vs 25.0%; P=0.039 ); annualized flare rate was numerically lower in Anifrolumab-treated patients ( 0.43 vs 0.64; rate ratio 0.67 [ 95% CI: 0.48, 0.94 ]; P=0.081 ).
Efficacy was further supported by numeric differences favoring Anifrolumab in multiple secondary endpoints ( unadjusted ), including SRI response ( 55.5% vs 37.3%; nominal P less than 0.001 ) and higher thresholds of SRI, time to onset of BICLA response sustained to week 52 ( hazard ratio [HR], 1.55; 95% CI: 1.11, 2.18; nominal P=0.011 ), and time to first flare ( HR, 0.65; 95% CI: 0.46, 0.91; nominal P=0.013 ).
In patients with high baseline IFN gene signature ( IFNGS ), Anifrolumab induced neutralization of IFNGS by week 12 ( median suppression 88.0% ) that was maintained through week 52.
Serum anti-dsDNA trended toward normalization with Anifrolumab.
The safety profile of Anifrolumab was similar to that of previous trials. Herpes zoster was more common in those receiving Anifrolumab ( 7.2% ) than placebo ( 1.1% ).
In contrast, serious adverse events were less frequent among Anifrolumab- than placebo-treated patients ( 8.3% and 17.0%, respectively ), as were adverse events leading to treatment discontinuation ( 2.8% and 7.1% ).
One death occurred in the Anifrolumab group ( pneumonia ).
Few patients ( 0.6% ) developed antidrug antibodies.
In conclusion, Anifrolumab was superior to placebo for multiple efficacy endpoints, including overall disease activity, skin disease, and oral corticosteroid tapering.
No new safety signals were identified.
TULIP-2 has demonstrated efficacy of Anifrolumab in moderate to severe systemic lupus erythematosus. ( Xagena )
Source: ACR/ARP Annual Meeting, 2019