Treatment of Juvenile Idiopathic Arthritis:Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis
Treatment
Table 3. General medication recommendations for children and adolescents with JIA and polyarthritis
NSAIDs
DMARDs
Glucocorticoids
- Bridging therapy may be of most utility in the setting of limited mobility and/or significant symptoms.
Biologic DMARDs
- In children and adolescents with JIA and polyarthritis, initiating treatment with a biologic combination therapy with a DMARD is conditionally recommended over biologic monotherapy.
Physical therapy and occupational therapy
- In children and adolescents with JIA and polyarthritis who have or are at risk of functional limitations, using physical therapy and/or occupational therapy is conditionally recommended.
Table 4. General guidelines for the initial and subsequent treatment of children and adolescents with JIA and polyarthritisa,b
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 toTNFi, 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.
Initial therapy
All patients
Patients without risk factors:b
Patients with risk factors:
- Initial biologic therapy may be considered for patients with risk factors and involvement of high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, and/or those judged by their physician to be at high risk of disabling joint damage.
Subsequent therapy: Low disease activity (cJADAS-10 ≤2.5 and ≥1 active joint)
For children receiving a DMARD and/or biologic:
- Escalation of therapy may include: Intra-articular glucocorticoid injection(s), optimization of DMARD dose, trial of methotrexate if not done, and adding or changing biologic.
Subsequent therapy: Moderate/high disease activity (cJADAS-10 >2.5)
If patient is receiving DMARD monotherapy:
If patient is receiving first TNFi (± DMARD):
- A second TNFi may be appropriate for patients with good initial response to their first TNFi (i.e., secondary failure).
If patient is receiving second biologic:
Table 5. Recommendations for the initial and subsequent treatment of children and adolescents with JIA and sacroiliitis
In children and adolescents with active sacroiliitis despite treatment with NSAIDs:
Glucocorticoids
In children and adolescents with active sacroiliitis despite treatment with NSAIDs:
- Bridging therapy may be of most utility in the setting of high disease activity, limited mobility, and/or significant symptoms.
Physical therapy
Table 6. Recommendations for the initial and subsequent treatment of children and adolescents with JIA and enthesitis
In children and adolescents with active enthesitis despite treatment with NSAIDs:
- Bridging therapy may be of most utility in the setting of high disease activity, limited mobility, and/or significant symptoms.
Physical therapy
Recommendation Grading
Overview
Title
Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis
Authoring Organization
American College of Rheumatology
Publication Month/Year
April 25, 2019
Last Updated Month/Year
November 7, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non‐systemic polyarthritis, sacroiliitis, or enthesitis.
Target Patient Population
Children with juvenile idiopathic arthritis
PICO Questions
In children and adolescents with JIA and polyarthritis, should methotrexate subcutaneous (SQ) or methotrexate oral (PO) be recommended?
In children and adolescents with JIA and polyarthritis, should methotrexate or leflunomide be recommended?
In children and adolescents with JIA and polyarthritis, should methotrexate or sulfasalazine be recommended?
In children and adolescents with JIA and polyarthritis and LDA (risk factor irrespective), should adding a limited course of prednisone (e.g. bridging/dosing TBD) to initial therapy versus not adding prednisone be recommended?
In children and adolescents with JIA and polyarthritis and moderate/ HDA (risk factor irrespective), should adding a limited course of prednisone (e.g., bridging/dosing TBD) to initial therapy versus not adding prednisone be recommended?
In children and adolescents with JIA and polyarthritis and LDA (risk factor irrespective) with initial non-biologic DMARD therapy, should treatment with chronic low dose prednisone (e.g., 0.2 mg/kg/day or max 10 mg day) versus adding a biologic be recommended?
In children and adolescents with JIA and polyarthritis and LDA (risk factor irrespective) with biologic therapy (+/- non-biologic DMARD), should adding treatment with chronic low dose prednisone (e.g., 0.2 mg/kg/day or max 10 mg day) versus switching biologic be recommended?
In children and adolescents with JIA and polyarthritis and moderate/HDA (risk factor irrespective) with biologic therapy (+/- non biologic DMARD), should adding treatment with chronic low dose prednisone (e.g., 0.2 mg/kg/day or max 10 mg day) versus switching biologic be recommended?
In children and adolescents with JIA and polyarthritis and active disease (risk factor and current/prior treatment irrespective), should treatment with intraarticular glucocorticoids versus no treatment with intraarticular glucocorticoids be recommended?
In children and adolescents with JIA and polyarthritis, should treatment with intraarticular triamcinolone acetonide versus triamcinolone hexacetonide be recommended?
In children and adolescents with JIA and polyarthritis, should etanercept monotherapy versus etanercept + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis, should adalimumab monotherapy versus adalimumab + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis, should infliximab monotherapy or infliximab + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis, should golimumab monotherapy versus golimumab + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis, should abatacept monotherapy versus abatacept + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis, should tocilizumab monotherapy versus tocilizumab + non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis on NSAID therapy and no risk factors, should continued NSAID monotherapy versus addition of non-biologic DMARD as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with triple non-biologic DMARD versus methotrexate monotherapy as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis, no risk factors, should initial therapy with triple non-biologic DMARD or TNFi as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with non-biologic DMARD versus TNFi as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with non-biologic DMARD versus abatacept as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with non-biologic DMARD versus tocilizumab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with TNFi versus tocilizumab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with TNFi versus abatacept as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis and no risk factors, should initial therapy with abatacept versus tocilizimab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors receiving NSAIDs, should continued NSAID monotherapy versus the addition of non-biologic DMARD as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should triple non-biologic DMARD versus methotrexate monotherapy as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should triple non-biologic DMARD versus TNFi as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with non-biologic DMARD versus TNFi as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with non-biologic DMARD versus abatacept as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with non-biologic DMARD versus tocilizumab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with TNFi versus tocilizumab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with TNFi versus abatacept as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis plus risk factors, should initial therapy with abatacept versus tocilizumab as initial therapy be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) and no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding TNFi to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) and no risk factors, receiving non-biologic DMARD, should changing to triple non-biologic DMARD therapy versus adding TNFi to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) and no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding abatacept to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) and no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding tocilizumab to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) and no risk factors, receiving TNFi, should changing to second drug within same class (TNFi) versus changing to OBRM be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) plus risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding TNFi to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) plus risk factors, receiving non-biologic DMARD, should changing to triple non-biologic DMARD therapy versus adding TNFi to original non-biologic DMARD be recommended?
. In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) plus risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding abatacept to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) plus risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding tocilizumab to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with low disease activity (cJADAS < 2.5) plus risk factors, receiving TNFi, should changing to second drug within same class (TNFi) versus changing to OBRM be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) and no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding TNFi to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/ high disease activity (cJADAS > 2.51), no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD or adding abatacept to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS > 2.51) and no risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding tocilizumab to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) and no risk factors, receiving TNFi (+/-non-biologic DMARD), should changing to second drug within same class (TNFi) versus changing to different drug in different OBRM class be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) and no risk factors, should rituximab versus 3rd class OBRM approved for JIA be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) plus risk factors, receiving non-biologic DMARD monotherapy, should changing to second non-biologic DMARD versus adding TNFi to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS > 2.51) plus risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding abatacept to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS > 2.51) plus risk factors, receiving non-biologic DMARD, should changing to second non-biologic DMARD versus adding tocilizumab to original non-biologic DMARD be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) plus risk factors, receiving TNFi (+/-non-biologic DMARD), should changing to second drug within same class (TNFi) versus changing to different drug in different OBRM class be recommended?
In children and adolescents with JIA and polyarthritis with moderate/high disease activity (cJADAS> 2.51) plus risk factors, should rituximab versus 3rd class OBRM approved for JIA be recommended?
In children and adolescents with JIA and polyarthritis regardless of disease activity and risk factors, should PT or no PT (regardless of concomitant medical therapy) be recommended?
In children and adolescents with JIA and polyarthritis regardless of disease activity and risk factors, should OT versus no OT (regardless of concomitant medical therapy) be recommended?
In children and adolescents with active sacroiliitis, should treatment with NSAID monotherapy versus no treatment with an NSAID in improving outcomes be recommended?
In children and adolescents with active sacroiliitis, is treatment with an NSAID in addition to ongoing therapy with a systemic DMARD or TNFi more effective than no treatment with an NSAID in improving outcomes?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with sulfasalazine compared to no treatment with sulfasalazine be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with methotrexate versus no treatment with methotrexate be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with TNFi compared to no treatment with TNFi be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with systemic corticosteroids versus no treatment with systemic corticosteroids be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with systemic corticosteroids versus sulfasalazine be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with intraarticular glucocorticoid injections of the sacroiliac joints versus no intraarticular glucocorticoids be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with intraarticular glucocorticoid injections of the sacroiliac joints versus sulfasalazine be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with intraarticular glucocorticoid injections of the sacroiliac joints versus TNFi be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with TNFi versus sulfasalazine be recommended?
In children and adolescents with active sacroiliitis despite treatment with NSAIDs, should treatment with TNFi versus systemic corticosteroids be recommended?
In children and adolescents with active enthesitis, should NSAID monotherapy versus no NSAIDs be recommended?
In children and adolescents with active enthesitis, is treatment with an NSAID in addition to ongoing therapy with a systemic DMARD or biologic more effective than no treatment with an NSAID in improving outcomes?
In children and adolescents with active enthesitis despite treatment with NSAIDs, should treatment with methotrexate versus TNFi be recommended?
In children and adolescents with active enthesitis despite treatment with NSAIDs, should treatment with methotrexate versus sulfasalazine be recommended?
In children and adolescents with active enthesitis despite treatment with NSAIDs, should treatment with sulfasalazine versus TNFi be recommended?
In children and adolescents with active enthesitis despite treatment with NSAIDs, should treatment with systemic glucocorticoids versus TNFi be recommended?
In children and adolescents with active sacroiliitis, should treatment with any form of PT versus no PT (regardless of concomitant medical therapy) be recommended?
In children and adolescents with active enthesitis, should any form of PT versus no PT (regardless of concomitant medical therapy) be recommended?
In children and adolescents with JIA with high risk of developing uveitis (oligoarthritis or rheumatoid factor seronegative polyarticular JIA, psoriatic JIA, ANA+), does screening more frequently than current guidelines decrease risk of developing ocular complications of uveitis?
In children and adolescents with JIA with inactive uveitis on stable therapy, what are the benefits and harms of ophthalmologic monitoring no longer than every 3 months until tapering compared to monitoring less frequently than every 3 months?
In children and adolescents with JIA with inactive uveitis who are tapering or discontinuing therapy, should ophthalmologic monitoring within 1 month after each change of topical steroid therapy versus monitoring less frequently be recommended?
In children and adolescents with JIA with inactive uveitis who are tapering or discontinuing therapy, should ophthalmologic monitoring 2 months after each change of systemic therapy versus monitoring less frequently be recommended?
In children and adolescents with JIA with active CAU in which therapy is being changed/escalated, should ophthalmologic monitoring visits no longer than every 2 weeks versus monitoring less frequently than every 2 weeks the appropriate frequency of ophthalmologic monitoring be recommended?
In children and adolescents with JIA with chronic uveitis controlled who have achieved control of their uveitis on systemic therapy and 1-2 drops/day of prednisolone acetate 1% (or equivalent), should weaning topical steroids first versus weaning systemic therapy first be recommended?
In children and adolescents with JIA with chronic uveitis controlled on (but still requiring) 1-2 drops/day of prednisolone acetate 1% (or equivalent) for at least 3 months, not on systemic therapy, should adding systemic therapy in order to taper topical steroids versus not adding systemic therapy and maintaining on topical steroids be recommended?
In children and adolescents with JIA with chronic uveitis controlled on (but still requiring) 1-2 drops/day of prednisolone acetate 1% (or equivalent), also on systemic therapy, should changing/escalating systemic therapy versus not changing systemic therapy and maintaining current therapy be recommended?
In children and adolescents with JIA with chronic active uveitis, irrespective of use of topical or systemic therapy, should giving intraocular steroid injections versus not giving intraocular steroid injections be recommended?
In children and adolescents with JIA with chronic active uveitis, should treatment with prednisolone acetate 1% topical drops versus difluprednate topical drops be recommended?
In children and adolescents with JIA with active CAU, should adding systemic steroids to topical steroid therapy for short term control versus not adding systemic steroids, which may include increasing frequency of topical steroids, be recommended?
In children and adolescents with JIA with new uveitis activity (either no prior uveitis or uveitis that was previously controlled, no active arthritis, and no topicals currently) regardless of current systemic therapy, should topical steroid therapy only and changing/escalating systemic therapy if unable to taper versus topical steroid therapy and changing/escalating systemic therapy immediately be recommended?
In children and adolescents with JIA with active CAU regardless of joint disease (assume uveitis guides therapy), should methotrexate PO versus methotrexate SQ be recommended?
In children and adolescents with JIA starting a systemic medication for their arthritis with no history of uveitis, what are the benefits and harms of etanercept compared to other TNFi in influencing the incidence of uveitis?
In children and adolescents with JIA with active arthritis and active CAU, what are the benefits and harms of starting etanercept compared to any other medication like methotrexate, other TNFi or other biologics?
In children and adolescents with JIA with inactive uveitis, off of topical steroids and needing a change in systemic therapy for active arthritis, should starting etanercept versus another TNFi be recommended?
In children and adolescents with JIA with active CAU regardless of joint disease (assume uveitis guides therapy), what are the benefits and harms of adalimumab compared to infliximab as first choice TNFi?
In children and adolescents with JIA with active CAU regardless of joint activity, should above standard dosing of infliximab (>10 mg/kg/dose every 4 weeks) versus standard JIA dosing be recommended?
In children and adolescents with JIA with active CAU regardless of joint activity, should above standard dosing of adalimumab (double dosing every 2 weeks or weekly dosing) versus standard JIA dosing be recommended?
In children and adolescents with JIA with active CAU on TNFi at standard JIA dose regardless of joint disease (assume uveitis guides therapy) who have failed one TNFi at standard dose, should escalating dose and/or frequency to above-standard dose versus switching to another TNFi be recommended?
In children and adolescents with JIA with active CAU who have failed first TNFi, regardless of arthritis activity (assume uveitis guides therapy), should switching to another TNFi versus switching to a biologic in another category be recommended?
In children and adolescents with JIA with severe active uveitis (2+ cells or more, or 1+ cells AND complications), should starting on MTX and a TNFi immediately versus methotrexate being trialed alone first be recommended?
In children and adolescents with JIA with active CAU, who have failed TNFi (one or more), should abatacept versus any other medication be recommended?
In children and adolescents with JIA with active CAU, who have failed TNFi (one or more), should tocilizumab versus any other medication be recommended?
In children and adolescents with JIA with active CAU, who have failed TNFi (one or more), should rituximab versus any other medication be recommended?
In children and adolescents with JIA with active CAU but no active arthritis, should mycophenolate versus any other medication be recommended?
In children and adolescents with JIA with active CAU but no active arthritis, should leflunomide versus any other medication be recommended?
In children and adolescents with JIA with active CAU but no active arthritis, what are the benefits and harms of cyclosporine compared to any other medication?
For children and adolescents with uveitis that is well controlled on systemic therapy only, when should therapy be weaned?
For children and adolescents with spondyloarthritis starting a TNFi for arthritis, does etanercept versus any other TNFi influence the risk of developing AAU or recurrent AAU?
For children and adolescents with spondyloarthritis starting a TNFi for arthritis, does the choice of TNFi influence the risk of developing AAU or recurrent AAU?
In children and adolescents with spondyloarthritis, is education regarding the warning signs of AAU more effective versus no education in decreasing delay in treatment, duration of symptoms, or complications of iritis?
In children and adolescents with spondyloarthritis, are TNFi monoclonal antibodies more effective in decreasing the occurrence or rate of recurrence of episodes of iritis versus etanercept?
In children and adolescents with spondyloarthritis who develop iritis while treated with a TNFi, is switching the TNFi more effective in decreasing recurrences of iritis versus continuing the same TNFi?
Inclusion Criteria
Male, Female, Adolescent, Child, Infant
Health Care Settings
Ambulatory, Childcare center, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment, Management
Diseases/Conditions (MeSH)
D001171 - Arthritis, Juvenile, D010372 - Pediatrics, D058566 - Sacroiliitis
Keywords
juvenile idiopathic arthritis, sacroiliitis, enthesitis, JIA, Non‐Systemic Polyarthritis
Source Citation
Ringold, S., Angeles‐Han, S.T., Beukelman, T., Lovell, D., Cuello, C.A., Becker, M.L., Colbert, R.A., Feldman, B.M., Ferguson, P.J., Gewanter, H., Guzman, J., Horonjeff, J., Nigrovic, P.A., Ombrello, M.J., Passo, M.H., Stoll, M.L., Rabinovich, C.E., Schneider, R., Halyabar, O., Hays, K., Shah, A.A., Sullivan, N., Szymanski, A.M., Turgunbaev, M., Turner, A. and Reston, J. (2019), 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res, 71: 717-734. doi:10.1002/acr.23870