Rilzabrutinib for Pemphigus: Does It Work?

observational-study PMID: 38493933

Quick Summary: Researchers studied a new drug called rilzabrutinib for people with pemphigus, a serious autoimmune disease. While the main goal wasn't fully met, the drug showed promise in helping people achieve remission and potentially reduce their need for steroids.

What The Research Found

The study looked at rilzabrutinib, a drug that works by targeting a specific protein in the body. The main goal was to see if it could help people with pemphigus go into complete remission (meaning their symptoms went away) while also taking a low dose of steroids. While the study didn't fully meet this goal, it showed that rilzabrutinib might help people achieve remission and potentially reduce their steroid use. The drug was also found to be safe, with similar side effects to a placebo (a sugar pill).

Study Details

Who was studied: 131 adults (ages 18-80) with moderate to severe pemphigus vulgaris or pemphigus foliaceus. These are autoimmune diseases that cause blistering of the skin and mucous membranes.

How long: The study lasted for 37 weeks (about 9 months).

What they took: Participants were randomly assigned to take either rilzabrutinib (400mg twice a day) or a placebo (an inactive pill) twice a day. All participants also took a low dose of steroids.

What This Means For You

If you have pemphigus, this research suggests that rilzabrutinib could be a new treatment option. It might help you:

Achieve remission (have your symptoms go away).

Potentially reduce your reliance on steroids, which can have serious side effects.

The drug appears to be safe, with side effects similar to a placebo.

Important Note: Rilzabrutinib is not yet widely available. Talk to your doctor about whether it might be a good option for you.

Study Limitations

The study's main goal wasn't fully met.

The study was relatively short (9 months), so we don't know the long-term effects of rilzabrutinib.

The study included a mix of pemphigus types (vulgaris and foliaceus), which may have affected the results.

The study's results were not statistically significant.

Key Findings

The PEGASUS phase 3 trial evaluated rilzabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, in 131 adults with moderate-to-severe pemphigus vulgaris (PV) or foliaceus (PF). The primary endpoint—complete remission from weeks 29–37 with corticosteroid (CS) ≤10 mg/day—was not met (24% vs. 18% for placebo, P = 0.45). However, prespecified sensitivity analyses using stricter CS criteria (≤5 mg/day) and including all observations showed improved remission rates with rilzabrutinib. Secondary endpoints (reduced CS use, prolonged remission duration, faster time to remission) showed numerical but nonsignificant benefits. Safety profiles were comparable between groups, with no major adverse events.

Study Design

This was a phase 3, double-blind, placebo-controlled randomized trial (observational design per source) conducted over 37 weeks. Participants (n = 131; 18–80 years) had moderate-to-severe PV/PF. Rilzabrutinib (400 mg, n = 65) or placebo (n = 66) was administered twice daily alongside CS ≤0.5 mg/kg/day.

Dosage & Administration

Rilzabrutinib was given orally at 400 mg twice daily (BID). Placebo matched the dosing schedule. Corticosteroid doses were capped at ≤0.5 mg/kg/day at baseline, with adjustments allowed per protocol.

Results & Efficacy

Primary Endpoint: 24% (13/54) of rilzabrutinib patients vs. 18% (10/55) with placebo achieved complete remission with CS ≤10 mg/day (not statistically significant, P = 0.45).
Secondary Endpoints:
Rilzabrutinib numerically reduced CS dependence (mean dose reduction not quantified).
Prolonged complete remission duration and faster time to first remission (exact effect sizes and P-values unspecified).
Sensitivity Analysis: Using CS ≤5 mg/day and including all observations, rilzabrutinib demonstrated improved efficacy, supporting BTK inhibition as a therapeutic strategy.

Limitations

The primary endpoint’s CS threshold (≤10 mg/day) may have been too lenient; stricter criteria (≤5 mg/day) showed benefit, suggesting dosing nuances matter.
Exclusion of remote observations (e.g., data from missed visits) might have diluted results.
Short duration (37 weeks) limits insights into long-term efficacy/safety.
Heterogeneity in pemphigus subtypes (PV vs. PF) and small sample size (n = 131) may reduce statistical power.

Clinical Relevance

This study suggests rilzabrutinib, a BTK inhibitor, may reduce corticosteroid reliance and improve remission in pemphigus, though the primary endpoint failed to reach significance. The safety profile aligns with placebo, making it a potentially viable option for autoimmune disease management. However, results emphasize the importance of corticosteroid tapering protocols and stricter outcome criteria in future trials. For supplement users, tyrosine kinase inhibition highlights a novel pathway for immune modulation, though rilzabrutinib itself is a prescription drug, not a dietary supplement. Further research is needed to confirm efficacy in larger, more diverse populations.

Source: PubMed (2024)