Saphnelo linked to reaching low disease activity status in SLE

Analysis of data from two Phase 3 trials yields promising results

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Adding Saphnelo (anifrolumab-fnia) to standard therapy in people with moderate to severe systemic lupus erythematosus (SLE) is linked to reaching a state of low disease activity faster and more frequently, according to an analysis of data from two Phase 3 clinical trials.

This low disease activity state was sustained for longer in Saphnelo-treated patients, with 15.3% of them achieving disease remission after one year compared with 7.6% of those given a placebo.

Overall, these findings support the use of Saphnelo in the “management of SLE, which may lead to optimised therapy approaches and result in long-term benefits for patients,” the researchers wrote.

The study, “Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus,” was published in the journal Annals of the Rheumatic Diseases.

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Remission — broadly defined as the complete absence of clinical disease activity — remains the goal of therapy in SLE. However, remission is seldom reached in real-world clinical practice with standard care medicines, and is even less frequent in clinical trials.

Attainment of the lupus low disease activity state (LLDAS) has been linked to improved outcomes, including protection against flares, low health-related quality of life (HRQoL), and death.

Saphnelo, a monoclonal human antibody marketed by AstraZeneca, is approved in several countries for the treatment of adults with moderate-to-severe SLE undergoing standard therapy. It targets and blocks the activity of type 1 interferon (IFN-1) receptor, which is involved in inflammation and the body’s immune response.

Data from two Phase 3 trials — TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) — have shown that adding Saphnelo to standard therapy lowered disease activity, as measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA).

The therapy also reduced the need for corticosteroids, and eased skin symptoms in people with moderate-to-severe SLE.

The MUSE trial

In the Phase 2 MUSE trial (NCT01438489), SLE patients treated with Saphnelo showed significantly greater attainment of LLDAS at week 52 (one year) compared with those on placebo.

In this study, researchers at AstraZeneca conducted a post hoc analysis of data from the two TULIP trials to assess whether Saphnelo treatment was linked to the attainment of LLDAS in patients with moderate-to-severe SLE.

Acquisition of LLDAS required the fulfillment of several criteria, including a score of four or lower in the SLE Disease Activity Index 2000 (SLEDAI-2K) scale, no major organ involvement, and no new disease activity. Also, the use of glucocorticoids, such as prednisone, could not exceed a daily dose of 7.5 mg, and non-standard immunosuppressants were not allowed.

In total, 819 patients were enrolled in TULIP-1 and TULIP-2. Patients were assigned randomly to receive one of the two doses of Saphnelo  — 300 mg (360 people) or 150 mg (93 people, in TULIP-1) — or a placebo (366 people).

At week 52, 205 patients (25%) attained LLDAS.

By week 52, a total of 186 of the 205 patients (90.7%) who attained LLDAS were deemed to be BICLA-responders. Among responders in the SLE responder index-4 (SRI-4), another measure of disease activity, 203 of 380 (53.4%) attained LLDAS by week 52.

In both BICLA and SRI-4 responders, nominally significant differences in LLDAS attainment were already seen at week 12.

Reports from patients

Researchers then evaluated patient-reported outcomes and HRQoL between LLDAS attainers and non-attainers at week 52. Results showed that LLDAS attainers reported greater improvements on perceived overall health when compared with LLDAS non-attainers.

LLDAS attainers also showed greater improvements in LupusQoL domains, including physical health and lessening of fatigue.

They then performed several analyses comparing patients given 300 mg of Saphnelo and those treated with a placebo. They assessed the percentage of patients attaining LLDAS, of those achieving a dual LLDAS-BICLA response, or a dual LLDAS-SRI-4 response.

Results showed that by week 52, 30% of Saphnelo-treated patients achieved LLDAS compared with 19.6% of those in the placebo group — a significant statistical difference. Also, the percentage of patients achieving a dual LLDAS-BICLA response was significantly higher among those treated with Saphnelo than in those given a placebo at all time points from week 24 to week 52.

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At week 52, dual LLDAS-BICLA was achieved by 27.8% of patients in the Saphnelo group and by 16.7% of those in the placebo group. Similarly, more patients given Saphnelo achieved the dual LLDAS-SRI-4 response at week 52 compared with placebo (30% vs. 19.1%).

Compared with placebo, Saphnelo-treated patients attained LLDAS significantly faster — at a median of 5.68 months — versus 6.46 months. The total percentage of time patients remained in LLDAS also favored Saphnelo over placebo (mean of 20% vs. 11.9%).

Saphnelo treatment also was associated with a significant increased likelihood — by twofold — of sustained LLDAS for at least three and five consecutive visits. After seven consecutive visits, this increased likelihood rose to nearly threefold.

Saphnelo treatment was linked to significantly higher remission rates. By week 52, 15.3% of Saphnelo-treated patients achieved remission compared with 7.6% of those on a placebo.

Overall, these findings support the usefulness of measuring LLDAS attainment in “SLE clinical trials and the potential to translate SLE clinical trial data into clinical practice to support treatment decisions,” the researchers wrote.

They also demonstrated that treatment with Saphnelo “results in significantly earlier and greater attainment of LLDAS and remission among patients who have moderate to severe SLE despite receiving standard of care,” they wrote.