Study in Focus 1:

Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis 

This phase 3 REGENCY trial was conducted to assess the efficacy and safety of Obinutuzumab (humanized type II anti CD 20 monoclonal antibody) in active lupus nephritis patients receiving background standard therapy (mycophenolate mofetil along with oral prednisolone at a target dose of 7.5 mg per day by week 12 and 5 mg per day by week 24). Out of 271 patients, 135 received intravenous infusions of Obinutuzumab (1000 mg on day 1 and at weeks 2, 24, 26, and 52, with or without a dose at 50 weeks) along with standard therapy, while 136 continued on standard therapy alone.

The Obinutuzumab group showed a statistically significant complete renal response at week 76 (complete renal response was defined as urine protein to creatinine ratio <0.5, eGFR at least 85% of baseline value, and no intercurrent event, which includes rescue therapy, treatment failure, death, or early trial withdrawal) compared to the standard therapy group (46.4% vs 33.1%) (p = 0.02). Additionally, the Obinutuzumab group performed better than the standard therapy group in key secondary endpoints (complete renal response at week 76 with prednisolone dosage of 7.5 mg per day or lower between weeks 64 and 76 and urine protein to creatinine ratio < 0.8 without intercurrent event).

In a specific subgroup analysis, the differences between the two groups was more evident in patients with baseline features indicative of high disease activity (urinary protein creatinine ratio > 3, low C3 C4, high anti ds DNA antibodies or coexistent class v lupus nephritis). Both the dosing regimens of Obinutuzumab (with or without dose at week 50) showed similar treatment responses. Therapy with Obinutuzumab was associated with a higher incidence of infections, principally respiratory tract infections. However, no unexpected safety signals were identified.

In conclusion, findings from this phase 3 REGENCY trial, support the hypothesis that profound B cell depletion is an effective treatment for patients with lupus nephritis.¹

Study in focus 2:

A phase 3 trial of Upadacitnib for Giant-Cell Arteritis

This phase 3 study (SELECT – GCA trial) assessed the efficacy and safety of Upadacitnib as compared with placebo, when combined with a glucocorticoid taper, to treat patients with active GCA. The study included patients aged more than 50 years with new-onset or relapsing GCA. It excluded patients with previous exposure to JAK inhibitors and who have had disease flares while receiving IL 6 inhibitors.

Out of a total of 428 patients, 209 received Upadacitnib at a dose of 15mg per day with a 26-week glucocorticoid taper, 107 received Upadacitnib at a dose of 7.5mg per day with a 26-week glucocorticoid taper, and 112 received placebo with a 52-week glucocorticoid taper. The 15mg Upadacitinib group was superior to placebo in achieving sustained remission at week 52. (Defined by the absence of signs or symptoms of GCA from week 12 through week 52 and adherence to the protocol specified glucocorticoid taper) (46.4% vs 29 %) (p = 0.002)

The 15mg Upadacitnib group fared better than the placebo group in key secondary endpoints (Sustained complete remission, time to disease flare, cumulative glucocorticoid exposure, and patient-reported outcomes). The 7.5 mg Upadacitnib group was not superior to placebo in achieving sustained remission at 52 weeks. Safety outcomes during the 52-week treatment period were similar in the Upadacitinib (15 mg and 7.5 mg) and placebo groups. No new safety concerns, including excess cardiovascular events, were noted in the Upadacitnib group. The incidence of cancer and venous thromboembolism did not differ significantly between the two groups.

The major limitations of the study were higher than expected percentage of patients who discontinued treatment in both the groups (Upadacitnib 26% vs placebo 37%) which was attributable to COVID pandemic during the study time, short duration of follow up (longer duration of follow up needed to assess safety of JAK inhibitors in elderly population) and exclusion of patients for whom IL 6 inhibitors were ineffective.

In conclusion, Upadacitinib at a dose of 15 mg with glucocorticoid taper was effective in treating active Giant cell arteritis, with no new safety concerns.²

References

1. Furie RA, Rovin BH, Garg JP, Santiago MB, Aroca-Martínez G, ZutaSantillán AE, et al. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med. 2025 Apr 17;392(15):1471-83.
2. Blockmans D, Penn SK, Setty AR, Schmidt WA, Rubbert-Roth A, Hauge EM, et al. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. N Engl J Med. Published online April 2, 2025.