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Anti-CD19 Monoclonal Antibody (B-Cell Depleting) Pregnancy: Avoid — B-cell depletion; potential for neonatal B-cell depletion if used in pregnancy.

Inebilizumab (Anti-CD19 — IgG4-Related Disease)

Brand names: Uplizna

Adult dose

Dose: 300 mg IV on Day 1 and Day 15 (loading); then 300 mg IV every 6 months (maintenance)
Route: IV infusion over 90 minutes
Frequency: Every 6 months (after loading doses)
Max: 300 mg per infusion
Targets CD19 — a broader B-cell marker than CD20 (rituximab). Depletes CD19+ B cells including CD19+/CD20- plasmablasts and plasma cells that escape rituximab. IgG4-RD is driven by pathogenic IgG4-secreting B cells — CD19 targeting addresses plasmablast escape. FDA approved 2024 for IgG4-RD. MHRA review ongoing.

Paediatric dose

Route:
Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment required.

Hepatic

No dose adjustment required.

Clinical pearls

  • MITIGATE trial (Stone et al. NEJM 2023): inebilizumab vs placebo in IgG4-RD — 87% relative reduction in IgG4-RD flares (HR 0.13; p<0.001); 40% achieved complete remission vs 23% placebo; dramatic efficacy across multiple organ systems (pancreas, bile ducts, orbits, kidneys, aorta). One of rheumatology's most striking RCT results. FDA approved on this single pivotal trial
  • CD19 vs CD20 advantage in IgG4-RD: rituximab (anti-CD20) is effective for IgG4-RD but plasmablasts — the key effector cells secreting pathogenic IgG4 — are CD19+/CD20-; they escape rituximab. Inebilizumab depletes the full CD19+ B-cell lineage including plasmablasts, explaining superior efficacy over rituximab in this disease
  • IgG4-RD presentation: typically fibro-inflammatory tumefactive lesions in multiple organs — pancreas (autoimmune pancreatitis, AIP type 1), bile ducts (cholangiopathy), orbits, salivary glands (Mikulicz), kidneys (tubulointerstitial nephritis), aorta (periaortitis). Serum IgG4 elevated in >60% but not diagnostic alone — histology with IgG4/IgG ratio >40% + storiform fibrosis is gold standard

Contraindications

  • Active hepatitis B (screen all patients — CD19 depletion can reactivate HBV; prophylactic antiviral required if core antibody positive)
  • Active serious infection
  • Live vaccines

Side effects

  • Infections (hypogammaglobulinaemia from B-cell depletion — monitor IgG levels; IVIG if severely low)
  • Infusion-related reactions (pre-medicate with corticosteroid, antihistamine, paracetamol)
  • Urinary tract infections
  • Nasopharyngitis
  • Lymphopenia

Interactions

  • Other B-cell depleting agents (rituximab — do not combine; additive hypogammaglobulinaemia)
  • Live vaccines (absolute — B-cell depletion prevents vaccine-induced antibody response)
  • Hepatitis B — prophylactic antivirals required if HBsAg+, HBcAb+ (see monitoring)

Monitoring

  • Serum IgG4 levels (biomarker — response monitoring)
  • Serum IgG levels (hypogammaglobulinaemia — monitor every 6 months)
  • HBV serology (HBsAg, HBcAb, HBV DNA) before and during treatment
  • Organ-specific monitoring (CT pancreas, LFTs, renal function, orbital imaging — per affected organs)
  • Infection surveillance (IgG supplementation if IgG <5 g/L)

Reference: BNFc; BNF 90; Stone et al. NEJM 2023 (MITIGATE trial); FDA Approval Uplizna 2024; ACR IgG4-RD Guidelines 2021; MHRA SPC (NMOSD indication). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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