ACUTE
early therapy
1st line – multidisciplinary
care and lifestyle modification
Patients with
incident or suspected JIA should be managed by a specialist paediatric
rheumatology multidisciplinary team.
Physiotherapy and
occupational therapy are encouraged in conjunction with medicines. Patients are
encouraged to participate in activities such as swimming and cycling, and
weight-bearing activities are indicated for those with a greater risk of low
bone mineral density. Moist heat can be a helpful adjunct modality
to address pain and stiffness.
Foot orthoses may
reduce pain and improve quality of life in children with JIA.
Adjunct – non-steroidal
anti-inflammatory drugs (NSAIDs)
Treatment
recommended for SOME patients in selected patient group
Primary options
naproxen : children >2 years of age: 10-20 mg/kg/day orally
given in divided doses every 12 hours
OR
nabumetone : consult specialist for guidance on dose
OR
diclofenac sodium : 3 mg/kg/day orally given in 2-4 divided doses
OR
meloxicam : children ≥2 years of age: 0.125 mg/kg orally once
daily, maximum 7.5 mg/day
OR
celecoxib : consult specialist for guidance on dose
OR
ibuprofen : 10 mg/kg orally three to four times daily
OR
indometacin : 0.5 to 1 mg/kg orally two to three times daily
OR
piroxicam : 0.2 to 0.4 mg/kg orally once daily
Occasionally used
for control of pain and stiffness but not disease modifying.
ONGOING
long-term therapy
1st line – methotrexate or
sulfasalazine
Primary options
methotrexate : 10 mg/square metre of body surface area
orally/subcutaneously once weekly on the same day of each week initially,
adjust dose according to response, maximum 20-30 mg/square metre of body
surface area/week
Secondary options
sulfasalazine : children >6 years of age: 30-50 mg/kg/day orally
given in 2 divided doses, maximum 2000 mg/day
Used when disease
has failed to respond to conventional medicines. Methotrexate is frequently the
first disease-modifying agent to be tried and is generally started within the
first few months in polyarticular disease. Methotrexate doses are increased
slowly and are held or lowered if liver function tests are elevated or if
absolute neutrophil counts are below 2.5 x 10⁹ L (2500/microlitre).
Methotrexate can be withdrawn once the clinician considers disease to be in clinical
remission.
Sulfasalazine may
be used for enthesitis-related disease. Sulfasalazine doses are increased
slowly weekly with careful FBC and comprehensive metabolic panel monitoring.
Sulfasalazine is to be avoided in individuals with a history of Stevens-Johnson
syndrome or hypersensitivities to sulfa drugs.
Plus – folic acid
Treatment
recommended for ALL patients in selected patient group
Primary options
folic acid : children 1-4 years of age: 0.15 mg orally once daily;
children 4-9 years of age: 0.2 mg orally once daily; children 9-14 years of age:
0.3 mg orally once daily; children >14 years of age: 0.4mg orally once daily
Folic acid is
useful to decrease side effects such as nausea, oral ulcers, and abnormal liver
enzymes.
Adjunct – symptom control +
lifestyle modification
Treatment
recommended for SOME patients in selected patient group
Primary options
naproxen : children >2 years of age: 10-20 mg/kg/day orally
given in divided doses every 12 hours
OR
nabumetone : consult specialist for guidance on dose
OR
diclofenac sodium : 3 mg/kg/day orally given in 2-4 divided doses
OR
meloxicam : children ≥2 years of age: 0.125 mg/kg orally once
daily, maximum 7.5 mg/day
OR
celecoxib : consult specialist for guidance on dose
OR
ibuprofen : 10 mg/kg orally three to four times daily
OR
indometacin : 0.5 to 1 mg/kg orally two to three times daily
OR
piroxicam : 0.2 to 0.4 mg/kg orally once daily
NSAIDs may be
used for control of pain and stiffness but are not disease modifying. Specific
NSAIDs are approved for children (e.g., tolmetin, naproxen, meloxicam, and
ibuprofen). However, many others are commonly used (e.g., nabumetone, diclofenac).
No specific NSAID is superior, and trial and error methods are used to identify
the most effective medicine for individual patients. Specialist
dosing guidance is required for nabumetone.
Physiotherapy and
occupational therapy are encouraged in conjunction with medicines. Patients are
encouraged to participate in activities such as swimming and cycling, and
weight-bearing activities are indicated for those with a greater risk of low
bone mineral density.
Adjunct – anti-emetics
Treatment
recommended for SOME patients in selected patient group
Primary options
ondansetron : children <4 years of age: 1-4 mg orally three
times daily depending on body surface area; children 4-11 years of age: 4 mg
orally three times daily; children ≥12 years of age: 8 mg orally three times
daily
Can be given to
relieve the side effects of nausea.
Adjunct – oral corticosteroids
Treatment
recommended for SOME patients in selected patient group
Primary options
prednisolone : 0.5 to 1 mg/kg orally once daily
Low-dose
corticosteroid therapy allows time for other agents to take effect during
active disease. It is important that corticosteroids are used judiciously in
children and are tapered as soon as possible.
Adjunct – intra-articular corticosteroids
Treatment
recommended for SOME patients in selected patient group
Primary options
triamcinolone acetonide : consult specialist for guidance on dose
Intra-articular corticosteroid
injections can be used alone or as part of a treatment plan involving other
systemic treatments. Radiographic assistance may be necessary for injecting
some joints. Younger children may need sedation, especially if multiple joints
are involved. It is important that corticosteroids are used judiciously in
children and are tapered as soon as possible. Doses usually depend on joint
size and other individual factors.
Adjunct – intravenous corticosteroids
Treatment
recommended for SOME patients in selected patient group
Primary options
methylprednisolone sodium succinate : 30 mg/kg/day intravenously given on three consecutive
days, repeated one week later, maximum 1 g/day
Patients with
systemic-onset juvenile idiopathic arthritis (SoJIA) may occasionally require
intravenous corticosteroids for overwhelming systemic inflammation or more
serious complications such as macrophage activation syndrome or pericarditis.
2nd line – TNF-alpha inhibitor, or interleukin
receptor antagonist, or fusion protein
Primary options
etanercept : (polyarticular JIA) children ≥2 years of age: 0.8
mg/kg subcutaneously once weekly, maximum 50 mg/week
OR
adalimumab : (polyarticular JIA) children ≥2 years of age and 10
to <15 kg body weight: 10 mg subcutaneously every 2 weeks; children ≥2 years
of age and 15 to <30 kg body weight: 20 mg subcutaneously every 2 weeks;
children ≥2 years of age and ≥30 kg body weight: 40 mg subcutaneously every 2
weeks
OR
tocilizumab : (polyarticular JIA) children ≥2 years of age and
<30 kg body weight: 10 mg/kg intravenously every 4 weeks, or 162 mg
subcutaneously every 3 weeks; children ≥2 years of age and ≥30 kg body weight:
8 mg/kg intravenously every 4 weeks, or 162 mg subcutaneously every 2 weeks;
(systemic JIA) children ≥2 years of age and <30 kg body weight: 12 mg/kg
intravenously every 2 weeks, or 162 mg subcutaneously every 2 weeks; children
≥2 years of age and ≥30 kg body weight: 8 mg/kg intravenously every 2 weeks, or
162 mg subcutaneously once weekly
OR
abatacept : (polyarticular JIA) dose depends on age, body weight,
and whether the intravenous or subcutaneous formulation is used; consult
specialist for guidance on dose
Secondary options
canakinumab : (systemic JIA) children ≥2 years of age and ≥7.5 kg
body weight: 4 mg/kg subcutaneously every 4 weeks, maximum 300 mg/dose
OR
infliximab : consult specialist for guidance on dose
OR
anakinra : consult specialist for guidance on dose
Tumour necrosis
factor (TNF)-alpha inhibitors include etanercept, adalimumab, and infliximab.
Etanercept is the
most widely used TNF-alpha inhibitor in younger children. Evidence
regarding safety and efficacy is limited; but studies have
demonstrated the longer-term safety and efficacy of etanercept in patients with
JIA. It should be avoided if uveitis is present.
Infliximab and
adalimumab are monoclonal antibodies. Pre-medication with
diphenhydramine, paracetamol, and a corticosteroid is advised before
administration of infliximab to minimise infusion-associated reactions. Over
70% of children receiving adalimumab in combination with methotrexate had a 70%
improvement in at least 3 of the American College of Rheumatology core-set
variables after 16 weeks of therapy. It is also effective in
patients with enthesitis-related arthritis in JIA. The
long-term tolerability of adalimumab in JIA has been demonstrated. Use of
infliximab is off-label for this indication.
Patients with
systemic disease may benefit from therapies including an interleukin-6 (IL-6)
receptor antagonist (e.g., tocilizumab), or an interleukin-1 (IL-1) receptor
antagonist such as anakinra or canakinumab.
Tocilizumab
blocks the activity of IL-6 (a pro-inflammatory cytokine), which exerts a
central role in systemic-onset juvenile idiopathic arthritis (SoJIA), and may
be useful in children with SoJIA who have not responded to NSAIDs and systemic
corticosteroids, and children with polyarticular JIA who have not responded to
conventional therapies. Tocilizumab is relatively well tolerated and has shown
efficacy for up to 52 weeks. Further studies are warranted to determine its
utility as a first-line option for SoJIA.
Canakinumab is
considered effective for the treatment of SoJIA with active systemic features;
however, long-term safety data are required.
Evidence suggests
that anakinra is safe and effective in some JIA patients, especially those with
systemic disease. It is currently being used successfully in a proportion
of patients with SoJIA. Use of anakinra is off-label for this
indication.
Abatacept is a
recombinant, fully humanised fusion protein used in those who do not respond
to, or are intolerant to, treatment with DMARDs (including TNF-alpha
inhibitors), and has shown efficacy and long-term safety. Improvements
in health-related quality of life were observed during a phase III,
double-blind, placebo controlled trial, providing real-life, tangible benefits
to children with JIA and their parents or carers.
Adjunct – pre-medication
Treatment
recommended for SOME patients in selected patient group
Primary options
diphenhydramine : children 2-5 years of age: 6.25 mg orally every 4-6
hours when required, maximum 37.5 mg/day; children 6-11 years of age: 12.5 to
25 mg orally every 4-6 hours when required, maximum 150 mg/day; children >12
years of age: 25-50 mg orally every 4-6 hours when required, maximum 300 mg/day
and
paracetamol : 10-15 mg/kg orally every 4-6 hours when required,
maximum 75 mg/kg/day
and
prednisolone : 0.5 to 1 mg/kg/day orally for 4-6 weeks
Pre-medication
with diphenhydramine, paracetamol, and corticosteroids is advised to minimise
infusion-associated reactions with infliximab. Methotrexate can
be withdrawn once the clinician considers that the disease is clinically in
remission.
It is important
that corticosteroids are used judiciously in children and are tapered as soon
as possible.
Adjunct – methotrexate plus folic acid
Treatment
recommended for SOME patients in selected patient group
Primary options
methotrexate : 10 mg/square metre of body surface area
orally/subcutaneously once weekly on the same day of each week initially,
adjust dose according to response, maximum 20-30 mg/square metre of body
surface area/week
and
folic acid : children 1-4 years of age: 0.15 mg orally once daily;
children 4-9 years of age: 0.2 mg orally once daily; children 9-14 years of
age: 0.3 mg orally once daily; children >14 years of age: 0.4 mg orally once
daily
If tolerated,
methotrexate should be used as an adjunct to adalimumab or infliximab in severe
refractory disease.
If inflammatory
bowel disease co-exists, methotrexate will help avoid the development of human
anti-chimeric antibodies. Methotrexate can be withdrawn once the
clinician considers that the disease is clinically in remission.
Folic acid is
useful to decrease side effects such as nausea, oral ulcers, and abnormal liver
enzymes.
Adjunct – symptom control + lifestyle
modification
Treatment
recommended for SOME patients in selected patient group
Primary options
naproxen : children >2 years of age: 10-20 mg/kg/day orally
given in divided doses every 12 hours
OR
nabumetone : consult specialist for guidance on dose
OR
diclofenac sodium : 3 mg/kg/day orally given in 2-4 divided doses
OR
meloxicam : children ≥2 years of age: 0.125 mg/kg orally once
daily, maximum 7.5 mg/day
OR
celecoxib : consult specialist for guidance on dose
OR
ibuprofen : 10 mg/kg orally three to four times daily
OR
indometacin : 0.5 to 1 mg/kg orally two to three times daily
OR
piroxicam : 0.2 to 0.4 mg/kg orally once daily
NSAIDs may be
used for control of pain and stiffness but are not disease modifying. Specific
NSAIDs are approved for children (e.g., tolmetin, naproxen, meloxicam, and
ibuprofen). However, many others are commonly used (e.g., nabumetone,
diclofenac). No specific NSAID is superior, and trial and error methods are
used to identify the most effective medicine for individual patients. Specialist
dosing guidance is required for nabumetone.
Physiotherapy and
occupational therapy are encouraged in conjunction with medicines. Patients are
encouraged to participate in activities such as swimming and cycling, and
weight-bearing activities are indicated for those with a greater risk of low
bone mineral density.
Adjunct – anti-emetics
Treatment
recommended for SOME patients in selected patient group
Primary options
ondansetron : children <4 years of age: 1-4 mg orally three times
daily depending on body surface area; children 4-11 years of age: 4 mg orally
three times daily; children ≥12 years of age: 8 mg orally three times daily
Can be given to
relieve the side effects of nausea.
Adjunct – oral corticosteroids
Treatment
recommended for SOME patients in selected patient group
Primary options
prednisolone : 0.5 to 1 mg/kg orally once daily
Low-dose
corticosteroid therapy allows time for other agents to take effect during
active disease. It is important that corticosteroids are used judiciously in
children and are tapered as soon as possible.
Adjunct – intra-articular corticosteroids
Treatment recommended
for SOME patients in selected patient group
Primary options
triamcinolone acetonide : consult specialist for guidance on dose
Intra-articular
corticosteroid injections can be used alone or as part of a treatment plan
involving other systemic treatments. Radiographic assistance may be necessary
for injecting some joints. Younger children may need sedation, especially if
multiple joints are involved. It is important that corticosteroids are used
judiciously in children and are tapered as soon as possible. Doses usually
depend on joint size and other individual factors.
Adjunct – intravenous corticosteroids
Treatment
recommended for SOME patients in selected patient group
Primary options
methylprednisolone sodium succinate : 30 mg/kg/day intravenously given on three consecutive
days, repeated one week later, maximum 1 g/day
Patients with
systemic-onset juvenile idiopathic arthritis (SoJIA) may occasionally require
intravenous corticosteroids for overwhelming systemic inflammation or more
serious complications such as macrophage activation syndrome or pericarditis.
Jacqui Clinch, Ripal Shah, (January 2019) Juvenile idiopathic arthritis, Available at: https://bestpractice.bmj.com/topics/en-gb/806 (Accessed: April 2019).