Cold agglutinin disease
disease diseaseOn this page
Also known as anemia, hemolytic, cold antibodyCADCASchronic cold agglutinin diseasecold agglutinin syndromecold antibody diseasecold antibody hemolytic anaemiacold antibody hemolytic anemia
Summary
Cold agglutinin disease (MONDO:0018922) is a disease and 16 clinical trials. Top therapeutic interventions include sutimlimab, pegcetacoplan, and eculizumab. A subtype of autoimmune hemolytic anemia, cold type — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Prevalence: 1-9 / 1 000 000 (Europe)
- Phenotypes (HPO): 14
- Clinical trials: 16
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-9 / 1 000 000 | Europe | Not yet validated |
Signs & symptoms
Clinical features (HPO)
14 HPO clinical features (Orphanet curated; top 14 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000980 | Pallor | Very frequent (80-99%) |
| HP:0001324 | Muscle weakness | Very frequent (80-99%) |
| HP:0001878 | Hemolytic anemia | Very frequent (80-99%) |
| HP:0002829 | Arthralgia | Very frequent (80-99%) |
| HP:0002960 | Autoimmunity | Very frequent (80-99%) |
| HP:0012378 | Fatigue | Very frequent (80-99%) |
| HP:0001744 | Splenomegaly | Occasional (5-29%) |
| HP:0002014 | Diarrhea | Occasional (5-29%) |
| HP:0002017 | Nausea and vomiting | Occasional (5-29%) |
| HP:0002240 | Hepatomegaly | Occasional (5-29%) |
| HP:0002315 | Headache | Occasional (5-29%) |
| HP:0002716 | Lymphadenopathy | Occasional (5-29%) |
| HP:0003418 | Back pain | Occasional (5-29%) |
| HP:0012086 | Abnormal urinary color | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | cold agglutinin disease |
| Mondo ID | MONDO:0018922 |
| Orphanet | 56425 |
| ICD-10-CM | D59.12 |
| SNOMED CT | 127055007 |
| UMLS | C1264008 |
| MedGen | 688249 |
| GARD | 0006130 |
| NORD | 775 |
| Is cancer (heuristic) | no |
Also known as: anemia, hemolytic, cold antibody · CAD · CAS · chronic cold agglutinin disease · cold agglutinin syndrome · cold antibody disease · cold antibody hemolytic anaemia · cold antibody hemolytic anemia
Disease family
This is a subtype of autoimmune hemolytic anemia, cold type. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › hematologic disorder › autoimmune disorder of blood › autoimmune hemolytic anemia › autoimmune hemolytic anemia, cold type › cold agglutinin disease
Related subtypes (1): paroxysmal cold hemoglobinuria
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
No druggable-target or therapeutic data for this disease’s cohort.
Clinical trials & evidence
Clinical trials
Clinical trials: 16.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| PHASE2 | 6 |
| Not specified | 5 |
| PHASE3 | 3 |
| PHASE1/PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03347422 | PHASE3 | COMPLETED | A Study to Assess the Efficacy and Safety of BIVV009 (Sutimlimab) in Participants With Primary Cold Agglutinin Disease Without A Recent History of Blood Transfusion |
| NCT05096403 | PHASE3 | COMPLETED | A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD) |
| NCT05132127 | PHASE3 | COMPLETED | Sutimlimab (BIVV009) for the Adult Participants With Cold Agglutinin Disease (CAD) Who Have Completed Phase 3 Studies (CARDINAL or CADENZA) in Japan |
| NCT05757570 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | An Open-label Study of Povetacicept in Participants With Autoimmune Cytopenias |
| NCT00373594 | PHASE2 | COMPLETED | Therapy for Chronic Cold Agglutinin Disease |
| NCT01303952 | PHASE2 | COMPLETED | Therapy of Chronic Cold Agglutinin Disease With Eculizumab |
| NCT01696474 | PHASE2 | COMPLETED | Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease |
| NCT02689986 | PHASE2 | COMPLETED | Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease |
| NCT03226678 | PHASE2 | COMPLETED | Study to Assess the Safety, Tolerability, Efficacy and PK of APL-2 in Patients With Warm Type Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD) |
| NCT05086744 | PHASE2 | TERMINATED | Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders |
| NCT02502903 | PHASE1 | COMPLETED | Safety, Tolerability and Activity of BIVV009 in Healthy Volunteers and Patients With Complement Mediated Disorders |
| NCT05791708 | Not specified | ACTIVE_NOT_RECRUITING | Cold Agglutinin Disease Real World Evidence Registry |
| NCT05931718 | Not specified | RECRUITING | Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia |
| NCT00960713 | Not specified | COMPLETED | The RITAI Cohort: An Observational Study on Rituximab Off-label Use for Auto-immune Disorders |
| NCT02022410 | Not specified | COMPLETED | CAS and Length of Hospital Stay After TKA |
| NCT04825145 | Not specified | COMPLETED | Preeclampsia and Contact Activation |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| SUTIMLIMAB | 4 | 3 |
| PEGCETACOPLAN | 4 | 2 |
| ECULIZUMAB | 4 | 1 |
| FLUDARABINE PHOSPHATE | 4 | 1 |
| IPTACOPAN | 4 | 1 |
| LUSPATERCEPT | 4 | 1 |
| POVETACICEPT | 2 | 1 |