adult-onset Still disease

Summary

adult-onset Still disease (MONDO:0019355) is a disease with 1 cohort gene (1 GWAS associations across 1 studies) and 13 clinical trials. Top therapeutic interventions include emapalumab, anakinra, and canakinumab.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• GWAS associations: 1
• Phenotypes (HPO): 59
• Clinical trials: 13

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Annual incidence	1-9 / 1 000 000	0.16	France	Validated
Annual incidence	1-9 / 1 000 000	0.13	Japan	Validated
Annual incidence	1-9 / 1 000 000	0.4	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.62	Turkey	Validated
Point prevalence	1-9 / 100 000	3.9	Japan	Validated
Point prevalence	1-9 / 100 000	6.9	Norway	Validated
Point prevalence	1-9 / 100 000	6.77	Turkey	Validated

Signs & symptoms

Clinical features (HPO)

59 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0000989	Pruritus	Very frequent (80-99%)
HP:0001369	Arthritis	Very frequent (80-99%)
HP:0001386	Joint swelling	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0001974	Leukocytosis	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0003281	Increased circulating ferritin concentration	Very frequent (80-99%)
HP:0003565	Elevated erythrocyte sedimentation rate	Very frequent (80-99%)
HP:0005059	Arthralgia/arthritis	Very frequent (80-99%)
HP:0010783	Erythema	Very frequent (80-99%)
HP:0011227	Elevated circulating C-reactive protein concentration	Very frequent (80-99%)
HP:0011897	Neutrophilia	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002102	Pleuritis	Frequent (30-79%)
HP:0002202	Pleural effusion	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002716	Lymphadenopathy	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0005828	Transient pulmonary infiltrates	Frequent (30-79%)
HP:0008940	Generalized lymphadenopathy	Frequent (30-79%)
HP:0025406	Asthenia	Frequent (30-79%)
HP:0025439	Pharyngitis	Frequent (30-79%)
HP:0033050	Pharyngalgia	Frequent (30-79%)
HP:0040186	Maculopapular exanthema	Frequent (30-79%)
HP:6000933	Koebner Phenomenon	Frequent (30-79%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0001298	Encephalopathy	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0001733	Pancreatitis	Occasional (5-29%)
HP:0002018	Nausea	Occasional (5-29%)
HP:0002039	Anorexia	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002840	Lymphadenitis	Occasional (5-29%)
HP:0002923	Rheumatoid factor positive	Occasional (5-29%)
HP:0003119	Abnormal circulating lipid concentration	Occasional (5-29%)
HP:0003493	Antinuclear antibody positivity	Occasional (5-29%)
HP:0005528	Bone marrow hypocellularity	Occasional (5-29%)
HP:0006515	Interstitial pneumonitis	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0012156	Hemophagocytosis	Occasional (5-29%)
HP:0012544	Elevated circulating aldolase concentration	Occasional (5-29%)
HP:0012819	Myocarditis	Occasional (5-29%)
HP:0100773	Cartilage destruction	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	adult-onset Still disease
Mondo ID	MONDO:0019355
EFO	EFO:0007135
MeSH	D016706
Orphanet	829
DOID	DOID:14256
ICD-10-CM	M06.1
ICD-11	549009522
SNOMED CT	239920006, 68190001
UMLS	C0085253
MedGen	39007
GARD	0000436
MedDRA	10058493, 10064056
NORD	737
Is cancer (heuristic)	no

Also known as: adult Still’s disease · adult-onset Still disease · Adult-Onset Still’s Disease · adult-onset Still’s disease · AOSD · Still’s disease adult onset · Wissler-Fanconi syndrome

Data availability: 1 GWAS association (1 study) · 12 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone inflammation disease › arthritic joint disease › adult-onset Still disease

Related subtypes (12): chondrocalcinosis, transient arthritis, synovitis, osteoarthritis, periarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, reactive arthritis, polyarticular arthritis, infective arthritis, negative rheumatoid factor polyarthritis, hemophilic arthropathy

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11102024	1e-08	LINC01768 - CSF1	T	3.28

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010175	Chen YM	2020	70	0	Genetic Association and Expression Correlation between Colony-Stimulating Factor 1 Gene Encoding M-CSF and Adult-Onset Still’s Disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11102024	1	109888892	A>T	0.075	intron_variant	LINC01768 - CSF1	1e-08	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CSF1	HGNC:2432	ENSG00000184371	P09603	Macrophage colony-stimulating factor 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF1	Macrophage colony-stimulating factor 1	Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSF1	Other/Unknown	no		MCSF-1, 4_helix_cytokine-like_core

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adipose tissue of abdominal region	1
omental fat pad	1
peritoneum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF1	223	ubiquitous	marker	omental fat pad, peritoneum, adipose tissue of abdominal region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CSF1	3,476

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSF1	P09603	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Other interleukin signaling	1	475.8×	0.008	CSF1
Signaling by CSF1 (M-CSF) in myeloid cells	1	346.1×	0.008	CSF1
Interleukin-10 signaling	1	233.1×	0.008	CSF1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.008	CSF1
Post-translational protein phosphorylation	1	100.2×	0.012	CSF1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	CSF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of macrophage derived foam cell differentiation	1	16852.0×	8e-04	CSF1
mammary gland fat development	1	16852.0×	8e-04	CSF1
positive regulation of macrophage colony-stimulating factor signaling pathway	1	16852.0×	8e-04	CSF1
positive regulation of odontogenesis of dentin-containing tooth	1	8426.0×	8e-04	CSF1
monocyte homeostasis	1	5617.3×	8e-04	CSF1
macrophage colony-stimulating factor signaling pathway	1	5617.3×	8e-04	CSF1
mammary duct terminal end bud growth	1	5617.3×	8e-04	CSF1
macrophage homeostasis	1	5617.3×	8e-04	CSF1
positive regulation of macrophage migration	1	5617.3×	8e-04	CSF1
positive regulation of mononuclear cell proliferation	1	4213.0×	9e-04	CSF1
myeloid leukocyte migration	1	4213.0×	9e-04	CSF1
osteoclast proliferation	1	3370.4×	9e-04	CSF1
developmental process involved in reproduction	1	3370.4×	9e-04	CSF1
positive regulation of microglial cell migration	1	2808.7×	0.001	CSF1
monocyte activation	1	1872.4×	0.001	CSF1
microglial cell proliferation	1	1872.4×	0.001	CSF1
neutrophil homeostasis	1	1532.0×	0.001	CSF1
positive regulation of monocyte differentiation	1	1532.0×	0.001	CSF1
branching involved in mammary gland duct morphogenesis	1	1404.3×	0.001	CSF1
regulation of ossification	1	1203.7×	0.002	CSF1
positive regulation of macrophage differentiation	1	1203.7×	0.002	CSF1
positive regulation of protein metabolic process	1	991.3×	0.002	CSF1
positive regulation of Ras protein signal transduction	1	887.0×	0.002	CSF1
positive regulation of macrophage derived foam cell differentiation	1	842.6×	0.002	CSF1
positive regulation of macrophage chemotaxis	1	802.5×	0.002	CSF1
monocyte differentiation	1	802.5×	0.002	CSF1
positive regulation of cell-matrix adhesion	1	674.1×	0.002	CSF1
positive regulation of osteoclast differentiation	1	581.1×	0.002	CSF1
positive regulation of multicellular organism growth	1	495.6×	0.003	CSF1
macrophage differentiation	1	468.1×	0.003	CSF1

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Anakinra	Phase 3 (in late-stage trials)
Canakinumab	Phase 3 (in late-stage trials)
Emapalumab	Phase 3 (in late-stage trials)
Goflikicept	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Tadekinig Alfa, Tocilizumab.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CSF1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CSF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE3	4
PHASE2	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04717635	PHASE3	COMPLETED	Study of Efficacy and Safety of Canakinumab in Japanese Patients With AOSD
NCT05001737	PHASE3	COMPLETED	Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still’s or SLE
NCT05432960	PHASE3	WITHDRAWN	Efficacy and Safety Clinical Study of RPH-104 in Adult Onset Still’s Disease (AOSD)
NCT06497491	PHASE3	COMPLETED	An Efficacy and Safety Study of GNR-086 (Canakinumab Biosimilar) and Ilaris® in Patients With Adult-onset Still’s Disease
NCT01033656	PHASE2	COMPLETED	Treatment of Refractory Adult-onset Still’s Disease With Anakinra: a Randomized Study
NCT03311854	PHASE2	COMPLETED	A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still’s Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
NCT04752371	PHASE1	TERMINATED	A Study to Evaluate Camoteskimab in Participants With Still’s Disease
NCT04402086	Not specified	RECRUITING	Rheumatology Patient Registry and Biorepository
NCT07151157	Not specified	ACTIVE_NOT_RECRUITING	Therapeutic Value of Sirolimus in Refractory Adult-Onset Still’s Disease
NCT07517250	Not specified	RECRUITING	A Study on the Use of Canakinumab Among Familial Mediterranean Fever and Still’s Disease Patients
NCT03276650	Not specified	COMPLETED	Admission of Adult-onset Still Disease Patients in the ICU
NCT03651193	Not specified	UNKNOWN	Multi-center Registration Study of Adult Onset Still’s Disease in Chinese Population
NCT04750863	Not specified	COMPLETED	Evaluation of Adult Onset Still Disease Classification Criteria and Differential Diagnosis at Eighteen Months of Follow-up

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EMAPALUMAB	4	2
ANAKINRA	4	1
CANAKINUMAB	4	1
GOFLIKICEPT	3	1
CAMOTESKIMAB	2	1
CHEMBL5220618	0	1