Four-Year Data Confirm Anifrolumab Efficacy in Lupus

Systemic lupus erythematosus (SLE) patients in the registration trials for anifrolumab (Saphnelo) who were followed for 4 years showed sustained improvement in hematologic and serologic parameters, as well as clinical symptom relief, researchers said.

Mean lymphocyte counts rose by more than 0.3 GI/L from baseline during the primary 52-week treatment period, gaining another 0.1 GI/L with additional treatment and remaining near that level through 4 years of follow-up, according to Edward Vital, PhD, of the University of Leeds in England, and colleagues. Meanwhile, little to no change in lymphocyte counts was seen in patients who continued on placebo.

Hemoglobin levels didn’t change much during the first year of anifrolumab therapy, but then increased slowly by about 4 g/L as follow-up continued, while participants on placebo saw decreases of 2-4 g/L over time, the researchers reported in ACR Open Rheumatology.

Platelet counts and C3 and C4 complement levels also improved more with anifrolumab than with placebo, Vital and colleagues reported. Meanwhile, anti-double stranded DNA antibody titers were largely stabilized with the active drug whereas they showed increases during the first 3 years of follow-up before coming back down to baseline during the final 52 weeks.

Another key finding was that improvements in these parameters were strongly associated with clinical improvement, irrespective of which treatment participants received, the researchers noted. Those achieving so-called BICLA responses, which require specified levels of improvement across major symptom domains, showed greater increases in lymphocytes at all time points than did nonresponders; platelet counts and hemoglobin levels were improved more in BICLA responders at most but not all assessments.

These findings suggest that “anifrolumab therapy may reduce pathogenic inflammation while also improving biomarkers that denote overall immune health,” Vital’s team wrote. “These improvements may be relevant to a wider range of other long-term outcomes important to patients’ health and quality of life.”

Anifrolumab is an interferon type 1 receptor antagonist, the only drug of this kind approved for SLE. It was mainly tested in two phase III trials called TULIP 1 and 2, with participants in both then entering a long-term extension. A total 358 were treated with anifrolumab at 300 mg every 4 weeks; 178 were randomized to placebo and continued on it during the extension. Participants also received standard background medications such as hydroxychloroquine for lupus throughout, and these could be added or adjusted during the extension.

At the original trials’ baseline, about 30% of participants had hemoglobin levels rated as low (<120 g/L), some 40% had low lymphocyte counts (<1 GI/L), and low platelet counts (<150 GI/L) were seen in 10%. About 40% of the sample were positive for anti-double stranded DNA and 36% were low in C3 complement. Just under one-quarter had low C4 levels.

Other findings from the study included numerically greater (but short of statistical significance) increases in neutrophil counts with anifrolumab versus placebo, and were greater still among patients with baseline neutropenia. Titers of immunoglobulins A, G, and M all declined more with anifrolumab than placebo — but the differences also didn’t reach statistical significance.

Limitations to the study included that not all of the original trial samples entered the long-term extension, and many dropped out during it, especially in the placebo group. Also, the findings related to platelets were uncertain because of the small number of participants with low baseline levels.