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 with the phrase: “In children and adolescents with JIA and active 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 biologic, recognizing that there are situations where initial therapy that includes a biologic may be preferred (PICO B.4). 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.	Low
Subsequent Therapy - Low Disease Activity (cJADAS10 ≤ 2.5 and at least 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). Escalation of therapy may include: Intraarticular glucocorticoid injection(s), optimization of DMARD dose, trial of methotrexate if not done, and adding or changing biologic.	Very low
Subsequent Therapy – Moderate/High Disease Activity (cJADAS10 > 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). A second TNFi may be appropriate for patients with good initial response to their first TNFi (i.e., secondary failure).	Very low
If patient is receiving second biologic:
Using TNFi, abatacept, or tocilizumab (depending upon prior biologics received) is conditionally recommended over rituximab (PICO B.10).	Very low

^*TNFi = tumor necrosis factor alpha inhibitor (etanercept, adalimumab, infliximab, golimumab).

^†Risk factors include presence of any of the following: positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, or presence of joint damage. The clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10) was used to define low disease activity (≤ 2.5 with ≥ 1 active joint) versus high/moderate disease activity (> 2.5). This is suggested as a general parameter, and the cJADAS-10 value should always be interpreted within the clinical context. 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 child, including discussion of recommended treatments and potential alternatives, is recommended when initiating or escalating treatment.