π¨ Breaking down the REGENCY trial π¨
A Phase 3 RCT evaluating obinutuzumab (Obi) in lupus nephritis (LN). Let's dive into the study design, key findings, and the dosing regimens! π§΅β¬οΈ
A Phase 3 RCT evaluating obinutuzumab (Obi) in lupus nephritis (LN). Let's dive into the study design, key findings, and the dosing regimens! π§΅β¬οΈ
1/ π₯ Study Design
πΉ Adults w/ biopsy-proven active proliferative LN (Class III/IV, w/ or w/o Class V)
πΉ Randomized 1:1 to Obi + MMF + steroids vs. Placebo + MMF + steroids
πΉ Primary endpoint: Complete Renal Response (CRR) at Wk 76
πΉ Key secondary: CRR w/ low prednisone
πΉ Adults w/ biopsy-proven active proliferative LN (Class III/IV, w/ or w/o Class V)
πΉ Randomized 1:1 to Obi + MMF + steroids vs. Placebo + MMF + steroids
πΉ Primary endpoint: Complete Renal Response (CRR) at Wk 76
πΉ Key secondary: CRR w/ low prednisone
2/ π MMF Dosing
πΉ All pts received MMF
βοΈ Started at randomization (if not already on it)
βοΈ Target dose: 2.0β2.5 g/day by Wk 4
βοΈ Maintained through Wk 76
π No cyclophosphamide (CYC) arm! MMF was the main immunosuppressant.
πΉ All pts received MMF
βοΈ Started at randomization (if not already on it)
βοΈ Target dose: 2.0β2.5 g/day by Wk 4
βοΈ Maintained through Wk 76
π No cyclophosphamide (CYC) arm! MMF was the main immunosuppressant.
3/ π Obinutuzumab Dosing
πΉ 1000 mg IV at:
βοΈ Day 1
βοΈ Week 2
βοΈ Week 24
βοΈ Week 26
βοΈ Week 52
π Two Obi arms (differing by a dose at Wk 50) were pooled for analysis.
πΉ 1000 mg IV at:
βοΈ Day 1
βοΈ Week 2
βοΈ Week 24
βοΈ Week 26
βοΈ Week 52
π Two Obi arms (differing by a dose at Wk 50) were pooled for analysis.
4/ π₯ Glucocorticoid Dosing (IV + Oral)
πΉ Pulse IV methylprednisolone (β₯250 mg, max 3g in 4 wks pre-trial)
πΉ Oral prednisone taper:
βοΈ Start: 0.5 mg/kg/day (max 60 mg/day)
βοΈ Taper to β€7.5 mg/day by Wk 12
βοΈ Maintain 5 mg/day from Wk 24-80
πΉ Pulse IV methylprednisolone (β₯250 mg, max 3g in 4 wks pre-trial)
πΉ Oral prednisone taper:
βοΈ Start: 0.5 mg/kg/day (max 60 mg/day)
βοΈ Taper to β€7.5 mg/day by Wk 12
βοΈ Maintain 5 mg/day from Wk 24-80
5/ π Primary Outcome: Obi = Higher Renal Response!
βοΈ CRR at Wk 76
πΉ Obi: 46.4%
πΉ Placebo: 33.1%
β +13.4% (p = 0.02)
βοΈ CRR w/ Pred β€7.5 mg/day
πΉ Obi: 42.7%
πΉ Placebo: 30.9%
β +11.9% (p = 0.04)
βοΈ CRR at Wk 76
πΉ Obi: 46.4%
πΉ Placebo: 33.1%
β +13.4% (p = 0.02)
βοΈ CRR w/ Pred β€7.5 mg/day
πΉ Obi: 42.7%
πΉ Placebo: 30.9%
β +11.9% (p = 0.04)
6/ π Renal Function Preservation
βοΈ eGFR Change from Baseline to Wk 76
πΉ Obi: +2.31 mL/min/1.73mΒ²
πΉ Placebo: β1.54 mL/min/1.73mΒ²
π Obi pts had stable kidney function while placebo pts declined!
βοΈ eGFR Change from Baseline to Wk 76
πΉ Obi: +2.31 mL/min/1.73mΒ²
πΉ Placebo: β1.54 mL/min/1.73mΒ²
π Obi pts had stable kidney function while placebo pts declined!
7/ β οΈ Safety Profile
πΉ Serious Adverse Events (SAEs)
βοΈ Obi: 32.4%
βοΈ Placebo: 18.2%
πΉ Most common SAEs
βοΈ Infections (esp. COVID-19, pneumonia, UTI)
βοΈ Infusion reactions
βοΈ Neutropenia (Obi 12.5% vs. Placebo 3.8%)
πΉ Serious Adverse Events (SAEs)
βοΈ Obi: 32.4%
βοΈ Placebo: 18.2%
πΉ Most common SAEs
βοΈ Infections (esp. COVID-19, pneumonia, UTI)
βοΈ Infusion reactions
βοΈ Neutropenia (Obi 12.5% vs. Placebo 3.8%)
8/ β οΈ Mortality & COVID-19 Risk
πΉ Deaths
βοΈ Obi: 3 (2 COVID-19, 1 nephrotic syndrome)
βοΈ Placebo: 1 (COVID-19)
π COVID-19 disproportionately affected Obi pts β underscores need for vaccination in LN!
πΉ Deaths
βοΈ Obi: 3 (2 COVID-19, 1 nephrotic syndrome)
βοΈ Placebo: 1 (COVID-19)
π COVID-19 disproportionately affected Obi pts β underscores need for vaccination in LN!
9/ π Who Benefited Most?
βοΈ UPCR β₯3 g/g at baseline β Greater benefit
βοΈ Low C3/C4 complement levels β More improvement
βοΈ Class IV LN (vs. Class III) β Better response
π Deep B-cell depletion helps high-risk LN pts!
βοΈ UPCR β₯3 g/g at baseline β Greater benefit
βοΈ Low C3/C4 complement levels β More improvement
βοΈ Class IV LN (vs. Class III) β Better response
π Deep B-cell depletion helps high-risk LN pts!
π Final Takeaways
β Obi improved renal outcomes in active LN
β Steroid-sparing effect (more Obi pts tapered to β€7.5 mg/day)
β Proteinuria reduction = better long-term kidney survival
β Infections (esp. COVID-19) are a key safety concern
β Obi improved renal outcomes in active LN
β Steroid-sparing effect (more Obi pts tapered to β€7.5 mg/day)
β Proteinuria reduction = better long-term kidney survival
β Infections (esp. COVID-19) are a key safety concern
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