Key Points
- Juvenile arthritis is one of the most common chronic diseases of childhood, with an estimated prevalence of 1 per 1,000 children.
- Following the exclusion of other known causes of synovitis, the term juvenile idiopathic arthritis (JIA) defines a heterogeneous collection of inflammatory arthritides of unknown etiology with onset prior to age 16 years and a minimum duration of 6 weeks.
- All forms of JIA are associated with decreased health-related quality of life and risk of permanent joint damage. The disease may persist into adulthood, causing ongoing significant morbidity and impaired quality of life.
- A number of treatments are available, including nonsteroidal antiinflammatory drugs (NSAIDs), systemic and intra-articular glucocorticoids, and nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs).
- Prompt initiation of appropriate therapy is of critical importance in preventing permanent damage and improving outcomes.
Treatment
Grade Definitions on Strength of Recommendation and Guide to Interpretation
Strength | For the patient | For the clinician | |
---|---|---|---|
Strong | “should use” or “should be used” | Most individuals in this situation would want the recommended course and only a small proportion would not. | Most individuals should receive the recommended course of action. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences. |
Conditional | “may be used” or “may consider” or “Y (less preferred drug) may be used instead of X (preferred drug)” or “may consider Y instead of X (preferred drug)” | The majority of individuals in this situation would want the suggested course, but many would not. | Different choices would be appropriate for different patients. Decision aids may be useful in helping individuals in making decisions consistent with their values and preferences. Clinicians should expect to spend more time with patients when working towards a decision. |
Grade Definitions of Quality and Certainty of the Evidence
Quality Grade | Definition |
---|---|
High | Very confident that the true effect lies close to that of the estimate of the effect. |
Moderate | Moderately confident in the effect estimate. The true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different. |
Low | Confidence in the estimate is limited. The true effect may be substantially different from the estimate of effect. |
Very low | Very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect. |
Table 1. Terms and definitionsa
Term | Definition |
---|---|
Polyarthritis population | Children with JIA and non-systemic polyarthritis (≥5 joints ever involved); may include children from ILAR JIA categories of polyarticular (rheumatoid factor positive or negative), extended oligoarticular, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. |
Risk factors | One or more of the following: positive rheumatoid factor, positive anti-cyclic citrullinated peptide antibodies, joint damage. |
Moderate/high disease activity | Clinical Juvenile Disease Activity Score based on the cJADAS-10 >2.5. |
Low disease activity | Clinical JADAS-10 ≤2.5 and ≥1 active joint. |
Sacroiliitis population | Patients with active sacroiliitis who will most likely be classified within the ILAR categories of enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis, but may include patients in any of the ILAR JIA categories. |
Active sacroiliitis | Prior or current magnetic resonance imaging findings consistent with sacroiliitis along with clinical examination findings consistent with sacroiliitis (e.g., pain with direct palpation of the sacroiliac joints) and/or patient-reported symptoms of inflammatory back pain. |
Enthesitis population | Patients with enthesitis (inflammation at tendon-to-bone insertion sites) who will most likely be from the ILAR categories of enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis, but may include patients from any of the ILAR JIA categories. |
Active enthesitis | Tenderness and/or swelling of the entheses determined to require medical treatment per the treatment provider. |
Table 2. Interventions included in the literature review
Intervention | Name/type |
---|---|
NSAIDs | Any |
DMARDs | Leflunomide, methotrexate, sulfasalazine, triple non-biologic DMARD (methotrexate, sulfasalazine, hydroxychloroquine) |
Biologics - TNFi | Adalimumab, etanercept, infliximab, golimumaba |
Biologics - Non-TNFib | Abatacept (CTLA-4Ig), tocilizumab (anti–interleukin-6 receptor), rituximab (anti-CD20) |
Glucocorticoids - Oral | Any |
Glucocorticoids - Intra-articular | Triamcinolone acetonide, triamcinolone hexacetonide, methylprednisolone acetate |
Other interventions | Physical therapy, occupational therapy |
b Evaluated for polyarthritis only.
Table 3. General medication recommendations for children and adolescents with JIA and polyarthritis
Recommendation | Level of Evidence |
---|---|
Each recommendation is preceded by the phrase: “In children and adolescents with JIA and active polyarthritis…” | |
NSAIDs | |
| Very low |
DMARDs | |
| Moderate (leflunomide); very low (sulfasalazine) |
| Very low |
Glucocorticoids | |
| Very low |
| Moderate |
| Very low |
| Very low |
| Very low |
Biologic DMARDs | |
| Very low (etanercept, golimumab); low (abatacept, tocilizumab); moderate (adalimumab) |
| Low |
Physical therapy and occupational therapy | |
| Low (physical therapy); very low (occupational therapy) |
Table 4. General guidelines for the initial and subsequent treatment of children and adolescents with JIA and polyarthritisa
Recommendationb | Level of Evidence |
---|---|
Each recommendation is preceded by the phrase: “In children and adolescents with JIA and active polyarthritis…” | |
Initial therapy | |
All patients | |
| Moderate |
| Low |
Patients without risk factors:b | |
| Low |
Patients with risk factors: | |
| Low |
Subsequent therapy: Low disease activity (cJADAS-10 ≤2.5 and ≥1 active joint) | |
For children receiving a DMARD and/or biologic: | |
| Very Low |
Subsequent therapy: Moderate/high disease activity (cJADAS-10 >2.5) | |
If patient is receiving DMARD monotherapy: | |
| Low |
| Low |
If patient is receiving first TNFi (± DMARD): | |
| Very low |
If patient is receiving second biologic: | |
| Very low |
b Risk factors include the presence of any of the following: positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, or presence of joint damage. An adequate trial of methotrexate was considered to be 3 months. If no or minimal response is observed after 6–8 weeks, it was agreed that changing or adding therapy may be appropriate. For the purposes of these recommendations, triple DMARD therapy is methotrexate, sulfasalazine, and hydroxychloroquine. The term biologic refers to TNFi, abatacept, or tocilizumab for each of the recommendations, with the exception of the recommendation for patients with JIA and polyarthritis and moderate or high disease activity despite a second biologic, which includes rituximab. Shared decision-making between the physician, parents, and patient, including discussion of recommended treatments and potential alternatives, is recommended when initiating or escalating treatment.
Figure 1. Summary of primary recommendations for the initial and subsequent treatment of children with JIA and active polyarthritis
Table 5. Recommendations for the initial and subsequent treatment of children and adolescents with JIA and sacroiliitis
Recommendation | Level of Evidence |
---|---|
In children and adolescents with active sacroiliitis, treatment with an NSAID is strongly recommended over no treatment with an NSAID. | Very low |
In children and adolescents with active sacroiliitis despite treatment with NSAIDs: | |
| Low |
| Low |
| Very low |
Glucocorticoids | |
In children and adolescents with active sacroiliitis despite treatment with NSAIDs: | |
| Very low |
| Very low |
Physical therapy | |
| Very low |
Table 6. Recommendations for the initial and subsequent treatment of children and adolescents with JIA and enthesitis
Recommendation | Level of Evidence |
---|---|
In children and adolescents with active enthesitis, NSAID treatment is strongly recommended over no treatment with an NSAID. | Very low |
In children and adolescents with active enthesitis despite treatment with NSAIDs: | |
| Low |
| Very low |
Physical therapy | |
| Very low |