Table 4.

General guidelines for the initial and subsequent treatment of 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 polyarthritis…”
Initial therapy
All patients
• Initial therapy with a DMARD is strongly recommended over NSAID monotherapy (PICO B.1).	Moderate
• Using methotrexate monotherapy as initial therapy is conditionally recommended over triple DMARD therapy (PICO B.2).	Low
Patients without risk factors:†
• Initial therapy with a DMARD is conditionally recommended over a biologic (PICO B.3).	Low
Patients with risk factors:
• Initial therapy with a DMARD is conditionally recommended over a biologic, recognizing that there are situations where initial therapy that includes a biologic may be preferred (PICO B.4).	Low
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:
• Escalating therapy is conditionally recommended over no escalation of therapy (PICO B.5, B.6).	Very low
Escalation of therapy may include: Intraarticular 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:
• Adding a biologic to original DMARD is conditionally recommended over changing to a second DMARD (PICO B.7).	Low
• Adding a biologic is conditionally recommended over changing to triple DMARD therapy (PICO B.8).	Low
If patient is receiving first TNFi (± DMARD):
• Switching to a non-TNFi biologic (tocilizumab or abatacept) is conditionally recommended over switching to a second TNFi (PICO B.9).	Very low
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:
• Using TNFi, abatacept, or tocilizumab (depending on prior biologics received) is conditionally recommended over rituximab (PICO B.10).	Very low

^*Disease activity (moderate/high and low) as defined by the clinical Juvenile Disease Activity Score based on 10 joints (cJADAS-10) is provided as a general parameter and should be interpreted within the clinical context. TNFi = tumor necrosis factor (etanercept, adalimumab, infliximab, golimumab) (see Table 3 for other definitions).

^†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 PICO B.10, 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.