Professor of Rheumatology, Northwestern Feinberg School of Medicine

Rosalind Ramsey-Goldman, MD

Fatigue, Pain, Daily Function: DZP’s Patient-Centered Impact in SLE, with Rosalind Ramsey-Goldman, MD

Dapirolizumab pegol (DZP), a novel, Fc-free anti-CD40L therapy, continues to demonstrate meaningful patient-centered benefits in systemic lupus erythematosus (SLE).

These findings are from a new analysis from the phase 3 PHOENYCS GO trial presented at the 

American College of Rheumatology (ACR) Convergence 2025

, held October 24–29 in Chicago, Illinois, by Rosalind Ramsey-Goldman, MD, Gallagher Research Professor of Rheumatology, Feinberg School of Medicine, Northwestern University.

The new data demonstrate that not only did DZP plus standard of care (SOC) meet its primary efficacy endpoint, achieving significantly higher rates of BILAG-based Composite Lupus Assessment (BICLA) response vs placebo +SOC at Week 48, but also produced broad and consistent improvements in health-related quality of life (HRQoL), as assessed by the LupusQoL instrument. 

spoke with Rosalind Ramsey-Goldman, MD, during the meeting to learn more about the importance of these findings—particularly as HRQoL gains increasingly shape modern lupus drug evaluation.

In PHOENYCS GO, 203 patients receiving DZP+SOC and 102 receiving placebo+SOC provided LupusQoL data. Baseline scores were comparable across groups. By Week 12, patients treated with DZP were already demonstrating superior improvements across multiple domains, gains that deepened through Week 48. 

Across 8 LupusQoL domains, DZP+SOC achieved significantly greater LS mean improvements versus placebo+SOC, including:

Fatigue: LS mean difference 10.5 (95% CI, 5.4-15.6); nominal 

Pain: LS mean difference 6.4 (95% CI, 1.1-11.7); nominal 

Physical health: LS mean difference 7.6 (95% CI, 2.9-12.3); nominal 

Emotional health: LS mean difference 7.1 (95% CI, 2.7-11.4); nominal 

Body image: LS mean difference 6.4 (95% CI, 0.6-12.2); nominal 

Intimate relationships: LS mean difference 6.3 (95% CI, –0.6 to 13.2); nominal 

Planning: LS mean difference 8.2 (95% CI, 2.3-14.1); nominal 

Burden to others: LS mean difference 10.9 (95% CI, 4.8-17.1); nominal 

Ramsey-Goldman emphasized that these outcomes are particularly meaningful because they capture aspects of disease not always reflected in traditional clinical endpoints. Fatigue, pain interference, emotional burden, and functional limitations often remain debilitating even when laboratory markers improve. The inclusion of patient-reported outcomes in trials like PHOENYCS GO ensures that treatment benefits extend beyond physician-based assessments.

Importantly, the HRQoL findings reinforce the clinical value of CD40L inhibition in SLE and support DZP as a therapy capable of improving both measurable disease activity and daily lived experience. 

"In more recent trials, they've been adding these patient reported outcomes as additional [data] to see how the patient responds to the drug, even if it's not the primary outcome... it's still important clinical information," Ramsey-Goldman said.

Ramsey-Goldman's reported disclosures include Ampel Solutions, AstraZeneca, Biogen, Cabaletta, Duke, Exagen Diagnostics, Merck, and SUNY Syracuse.

Touma Z, Aranow C, Parodis I, et al. Dapirolizumab Pegol Demonstrated Improvement in Quality of Life of Patients with Systemic Lupus Erythematosus: LupusQoL Results from a Phase 3 Trial. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #2441

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Ramsey-Goldman emphasized the importance of QoL in lupus, looking beyond disease scores.

Proof of Concept: Targeting Mitochondrial Dysfunction in SLE With NAC, with Rosalind Ramsey-Goldman, MD

N-acetylcysteine (NAC) shows promise as a novel therapeutic strategy for systemic lupus erythematosus (SLE), although these findings remain to be confirmed by the double-blind phase of the ongoing multicenter trial.

Data from the first phase of the trial were presented by Rosalind Ramsey-Goldman, MD, Gallagher Research Professor of Rheumatology, Feinberg School of Medicine, Northwestern University, at the 

, held October 24–29 in Chicago, Illinois.

Unlike immunosuppressants, NAC aims to correct core metabolic defects driving lupus pathogenesis rather than broadly suppressing the immune system. The therapy is designed to restore intracellular cysteine and glutathione (GSH) levels, thereby reducing mitochondrial oxidative stress, mTOR activation, inflammatory lineage skewing, and antinuclear autoantibody production. The trial uses an enriched-enrollment randomized-withdrawal design, with all eligible patients completing a 3-month open-label titration phase of NAC (2.4–4.8 g/day) prior to randomization into the blinded phase.

In the first 3 months of the study, NAC produced statistically significant reductions in global SLE disease activity among 68 patients. Mean SLEDAI scores decreased from 8.73 (SD, 3.093) at baseline to 4.91 (SD, 2.92) at month 3 (

 = 1.1×10⁻¹²), with a mean difference of 3.671 (SD, 3.201). BILAG total scores demonstrated an even larger shift, falling from 23.808 (SD 5.099) to 8.750 (SD 6.027; 

 = 1.9×10⁻²²), with a mean difference of 15.058 (SD, 8.424).

Importantly, NAC also improved patient-reported cognitive and fatigue symptoms in 54 participants. ADHD-Inattention scores improved from 19.259 (SD, 2.960) to 16.407 (SD, 7.449), a mean difference of 2.851 (SD 6.645; 

 = 1.5×10⁻²), and ADHD-Hyperactivity improved from 14.962 (SD, 7.530) to 13.185 (SD, 7.809), a mean difference of 1.777 (SD, 4.063; 

= 1.3×10⁻²). Physical fatigue decreased from 19.259 (SD, 2.960) to 16.092 (SD, 3.972), a mean difference of 3.166 (SD, 3.318; 

 = 2.5×10⁻⁸), while mental fatigue improved from 14.425 (SD, 4.574) to 12.092 (SD, 4.814), a mean difference of 2.333 (SD, 3.518; 

Adverse events included headache, nausea, gastrointestinal symptoms, constipation, and diarrhea and were transient and reversible. Eighteen participants withdrew during this phase, though only 1 withdrawal was attributed to adverse events.

Ramsey-Goldman emphasized that while these early, open-label results are encouraging, the ongoing double-blind phase will be essential to confirm NAC’s disease-modifying potential and determine whether this mitochondria-directed approach could offer a safer alternative to traditional immunosuppression in SLE.

"What NAC does is it replaces the chemicals that were missing so that the mitochondria function properly, so that the cell doesn't push itself toward overdrive or an inflammatory state, and it diminishes the antibodies that are causing the lupus [with] less side effects," Ramsey-Goldman said.

Ruchi FNU, Coman I, Blaker B, et al. Preliminary Analysis Of Open-Label Dose-Titration Phase Of SLE Treatment With N-Acetylcysteine (SNAC) Shows Evidence For Potential Improvement Of SLEDAI, BILAG, ADHD And Fatigue Scores In Patients With Active SLE. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #0657

Ramsey-Goldman discussed the potential of NAC for treating systemic lupus erythematosus.

Rosalind Ramsey-Goldman, MD

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