Table 4.
Medication monitoring*
| Recommendation | Certainty of evidence | PICO evidence report(s) basis | Page no(s). of evidence tables† |
|---|---|---|---|
| NSAIDs: Monitoring via CBC counts, LFTs, and renal function tests every 6–12 months is conditionally recommended. | Very low | PICO 30. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel, and urinalysis) for children receiving long-term daily NSAID treatment? | 144–145 |
| MTX: Monitoring via CBC counts, LFTs, and renal function tests within the first 1–2 months of usage and every 3–4 months thereafter is strongly recommended. | Very low | PICO 31. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel) for children being treated with MTX (oral or subcutaneous)? | 145–150 |
| Decreasing the MTX dosage or withholding MTX is conditionally recommended if a clinically relevant elevation in LFT results or decreased neutrophil or platelet count is found. | Very low | PICO 32. After MTX (oral or subcutaneous) is initiated, is there a recommended medication change in response to elevated LFT results and decreased neutrophil or platelet count? | 150–153 |
| Use of folic/folinic acid in conjunction with MTX is strongly recommended. | Very low | PICO 7. In children with oligoarticular JIA, should dietary or herbal interventions be recommended, in addition to whatever other therapeutic options are used, versus not recommending them? | 60 |
| SSZ: Monitoring via CBC counts, LFTs, and renal function tests within the first 1–2 months of usage and every 3–4 months thereafter is conditionally recommended. | Very low | PICO 33. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel) for children with JIA being treated with SSZ? | 153–155 |
| Decreasing the SSZ dosage or withholding SSZ is conditionally recommended if a clinically relevant elevation in LFT results or decreased neutrophil or platelet count is found. | Very low | PICO 34. After SSZ is initiated, is there a recommended medication change in response to elevated LFT results and decreased neutrophil or platelet count? | 155–157 |
| LEF: Monitoring via CBC counts and LFTs within the first 1–2 months of usage and every 3-4 months thereafter is conditionally recommended. | Very low | PICO 35. Should children with JIA receiving LEF have serum creatinine testing, urinalysis, CBC count, and LFTs before and during treatment, per manufacturer’s recommendations? |
157–158 |
| Altering LEF administration is conditionally recommended if a clinically relevant elevation in LFT results occurs (temporary withholding of LEF if the ALT level is >3 times the upper limit of normal [ULN]), as per the package insert. |
Very low | PICO 36. After LEF is initiated, should medication dosage be altered according to the package insert in response to elevated LFT results? | 158–159 |
| Baseline and annual retinal screening after starting HCQ are conditionally recommended. | Very low | PICO 37. Should children with JIA receiving treatment with HCQ have annual screening tests with automated visual fields, if age appropriate, plus spectral-domain optical coherence tomography, versus starting annual screening 5 years after treatment initiation? | 159 |
| HCQ: Monitoring via CBC counts and LFTs annually is conditionally recommended. |
Very low | PICO 38. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel) for children with JIA being treated with HCQ? | 159 |
| TNFi: Monitoring via CBC counts and LFTs annually is conditionally recommended. |
Very low | PICO 39. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel, and urinalysis) for children with JIA receiving TNFi treatment? |
160–161 |
| Abatacept: Doing no routine laboratory monitoring is conditionally recommended. |
Very low | PICO 40. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel, and urinalysis) for children with JIA receiving abatacept treatment? | 161–162 |
| Tocilizumab: Monitoring via CBC counts and LFTs within the first 1–2 months of usage and every 3–4 months thereafter is conditionally recommended. Monitoring of lipid levels every 6 months is conditionally recommended, as per the package insert. |
Very low | PICO 41. Should children with JIA receiving tocilizumab have serum creatinine testing, urinalysis, CBC count, and LFTs before and during treatment, per manufacturer’s recommendations? | 162 |
| Altering tocilizumab administration is conditionally recommended if monitoring reveals elevated LFT results (if 1–3 times the ULN, decrease the dosage or increase the interval between doses, if >3 times the ULN, withhold administration, if >5 times the ULN, discontinue treatment), neutropenia (500–1,000/mm3), or thrombocytopenia (50,000–100,000/mm3), as per the package insert. | Very low | PICO 42. After tocilizumab is initiated, should medication dosage be altered according to the package insert in response to elevated LFT results, neutropenia, and/or thrombocytopenia? | 163 |
| Anakinra: Monitoring via CBC counts and LFTs within the first 1–2 months of usage and every 3–4 months thereafter is conditionally recommended. | Very low | PICO 43. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel, and urinalysis) for children with JIA receiving anakinra treatment? | 163–164 |
| Canakinumab: Monitoring via CBC counts and LFTs within the first 1–2 months of usage and every 3–4 months thereafter is conditionally recommended. | Very low | PICO 44. Is there a recommended laboratory screening schedule (CBC count, comprehensive metabolic panel, and urinalysis) for children with JIA receiving canakinumab treatment? | 164 |
| Tofacitinib: Monitoring via CBC counts and LFTs within the first 1–2 months of usage and every 3–4 months thereafter is conditionally recommended. Monitoring of lipid levels 1–2 months after starting treatment is conditionally recommended, as per the package insert. Altering tofacitinib administration is strongly recommended if monitoring reveals laboratory abnormalities of concern. Specifically, medication should be discontinued if the hemoglobin level is <8 gm/dl or decreases by >2 gm/dl, or for severe neutropenia (<500/mm3) or lymphopenia (<500/mm3), as per the package insert. |
‡ | ‡ | ‡ |
*
PICO = Patient/Population, Intervention, Comparison, and Outcomes; NSAIDs = nonsteroidal antiinflammatory drugs; CBC = complete blood cell; LFTs = liver function tests; MTX = methotrexate; JIA = juvenile idiopathic arthritis; SSZ = sulfasalazine; LEF = leflunomide; ALT = alanine aminotransferase; ULN = upper limit of normal; HCQ = hydroxychloroquine; TNFi = tumor necrosis factor inhibitor.
†
In Supplementary Appendix 3, on the Arthritis & Rheumatology website at https://onlinelibrary.wiley.com/doi/10.1002/art.42036/abstract.
‡
Given recent approval for JIA and limited experience, recommendations are based on clinical trial, US Food and Drug Administration guidance, and evidence in adults.