Interleukin-6 in juvenile idiopathic arthritis

Figures & data

Figure 1. Juvenile idiopathic arthritis as a heterogenous disease. Juvenile idiopathic arthritis is an umbrella term of chronic arthritis of unknown etiology. It consists of seven types; systemic-onset arthritis, oligoarthritis, rheumatoid factor-negative polyarthritis, rheumatoid factor-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis and others. They are basically classified by the presence of arthrosynovitis or enthesitis. They have some common features but different characteristics in pathogenesis, genetic and epigenetic profile, clinical presentation, therapeutic response and comorbidity and prognosis.

Table 1. ILAR classification criteria for juvenile idiopathic arthritis (The edmonton revision 2001).

Category	Inclusions	Exclusions
Systemic-onset arthritis	Arthritis plus more than 2 week's fever and at least one of the following: Evanescent rash. Generalized lymphadenopathy. Enlargement of liver or spleen. Serositis.	(a) (b) (c) (d) (f)
Oligoarthritis	Arthritis in less than 5 joints during the first 6 months. *Arthritis with more than 4 joints after the first 6 months termed as extended Oligoarthritis. Otherwise, termed as persistent Oligoarthritis.	(a) (b) (c) (d) (e) (f)
Polyarthritis, RF-negative	Arthritis with 5 or more joints during the first 6 months: IgM rheumatoid factor negative.	(a) (b) (c) (d) (e) (f)
Polyarthritis, RF-positive	Arthritis with 5 or more joints during the first 6 months: IgM rheumatoid factor positive on at least two occasions at least 3 months apart.	(a) (b) (c) (e) (f)
Psoriatic arthritis	Arthritis plus psoriasis or Arthritis plus at least two of the following: Dactylitis. Nail pits or onycholysis. A positive family history of psoriasis in a first-degree relative.	(b) (c) (d) (e) (f)
Enthesitis-related arthritis	Arthritis plus enthesitis or Arthritis/Enthesitis plus at least two of the following: A positive past/present history of sacroiliac pain or inflammatory back pain. Presence of HLA-B27. A positive family history of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis, or acute anterior uveitis in a first-degree relative. Acute symptomatic anterior uveitis. Onset of arthritis in a boy after 6 year of age.	(a) (d) (e) (f)
Undifferentiated	Arthritis fulfilling no, or two or more categories.	none

Juvenile idiopathic arthritis is defined as arthritis of unknown etiology that begins before the 16^th birthday and persists for at least 6 weeks; other known conditions are excluded. Exclusion items: (a) Psoriasis or a positive history of psoriasis in the patient or a first-degree relative. (b) An HLA-B27 positive male beginning after the sixth birthday. (c) Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis, or acute anterior uveitis, or a positive history of one of these disorders in a first-degree relative. (d) IgM rheumatoid factor on at least two occasions at least 3 months apart. (e) The presence of systemic-onset juvenile idiopathic arthritis in the patient. (f) Arthritis fulfilling the two categories.

Figure 2. Key milestones in the development of IL-6 inhibitors for juvenile idiopathic arthritis. JIA: juvenile idiopathic arthritis; soJIA: systemic onset JIA; poly-JIA: polyarticular JIA; FDA: US Food and Drug Administration; EMA: European Medicines Agency; ACR: American College of Rheumatology; TCZ: tocilizumab; TCZ-SQ: TCZ with subcutaneous injection; SARIL: sarilumab.