DrugAlternative line2 diseases

Ibrutinib

BTK inhibitor

Response rate
Complete in case reports
Onset
2 weeks – 3 months
Route
Oral 420mg daily
Line
Alternative
IgM effect
Reduces IgM
Evidence level
default
Trial phase
Phase 4
Open Targets score
0.35

Used across diseases

DiseaseResponse rateLineEvidence
Schnitzler SyndromeComplete in case reportsAlternativedefault
Waldenström's Macroglobulinemia90% ORR; 73% MRR (previously treated)1stgreen

Evidence summary

The only drug shown to reduce both inflammatory symptoms AND IgM levels. Three case reports (2018–2022) demonstrate efficacy, including one MYD88 L265P-positive patient where IgMκ monoclonal protein declined — unique among all treatments.

Approved indications

Conditions for which Ibrutinib has regulatory approval (not specific to rare diseases covered here):

CLL/SLLMantle Cell LymphomaWaldenström's MacroglobulinemiacGVHD

Drug identifiers

DrugBankDB09053
ATC CodeL01EL01
Open TargetsCHEMBL1873475

Molecular targets

MoleculeRoleExpressionEvidence
MYD88TLR signalling adaptorL265P in ~30%moderate
BTKB-cell receptor kinaseActivemoderate
IgM (monoclonal)Diagnostic paraproteinPresent (obligate)established

Sources (3)

DetailsJani P et al. (2018) Ibrutinib for the management of Schnitzler syndrome: a case reportPubMed
DetailsClaves FP et al. (2021) Ibrutinib in Schnitzler syndrome: a case reportPubMed
DetailsHuang Y et al. (2022) Ibrutinib for MYD88 L265P-positive SchnitzlerDOI