Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany

Abstract

Background: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany.

Methods: We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany. Subsequently, via online surveys and teleconferences among pediatric rheumatologists with a special expertise in the treatment of SJIA, we identified current diagnostic and treatment approaches in Germany. Those were harmonized via the formulation of statements and, supported by findings from a literature search. Finally, an in-person consensus conference using nominal group technique was held to further modify and consent the statements.

Results: Up to 50% of patients diagnosed with SJIA in Germany do not fulfill the International League of Associations for Rheumatology (ILAR) classification criteria, mostly due to the absence of chronic arthritis. Our findings suggest that chronic arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a diagnosis of probable SJIA. Malignant, infectious and hereditary autoinflammatory diseases should be considered before rendering a diagnosis of probable SJIA. There is substantial variability in the initial treatment of SJIA. Based on registry data, most patients initially receive systemic glucocorticoids, however, increasingly substituted or accompanied by biological agents, i.e. interleukin (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred initial therapies for probable and definitive SJIA, including step-up patterns and treatment targets for the short-term (resolution of fever, decrease in C-reactive protein by 50% within 7 days), the mid-term (improvement in physician global and active joint count by at least 50% or a JADAS-10 score of maximally 5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive disease within 6 to 12 months), and an explicit treat-to-target strategy.

Conclusions: We developed consensus-based strategies regarding the diagnosis and treatment of probable or definitive SJIA in Germany.

Keywords: Biologics; Diagnosis; Glucocorticoids; Interleukin-1 blockade; Interleukin-6 blockade; Systemic juvenile idiopathic arthritis; Treat-to-target.

Fig. 1

Treatment targets for the treatment of systemic juvenile idiopathic arthritis. Treatments should be reached sequentially. The physician global assessment is scored on a scale of 0 to 10, where 0 represents lack of any disease activity and 10 represents maximal disease activity. The juvenile arthritis disease activity score (JADAS)-10 represents the sum of 4 individual scores, namely the physician global assessment (range 0–10), the patient or parent global assessment (range 0–10), the active joint count (range 0–10), and the normalized erythrocyte sedimentation rate after 1 h ([observed rate - 20]/100, i.e. values up to 20 mm/h are scored as 0 and values equal to or above 120 mm/h are scored as 10) or C-reactive protein (CRP; [observed CRP in mg/l – 10]/100, i.e. values up to 10 mg/l are scored as 0 and values equal to or above 110 mg/l are scored as 10)

Fig. 2

Treat-to-target consensus treatment strategy for the initial therapy of probable systemic juvenile idiopathic arthritis (SJIA). Maximal doses for glucocorticoids: i.v. methylprednisolone pulse therapy (20–30 mg/kg/day [max. 1000 mg/day) for 5 days or prednisolone equivalent 1–2 mg/kg/day (max. 80 mg/day). “Biologic” refers to anakinra, canakinumab or tocilizumab. Maximal doses for biologics: anakinra 8 mg/kg/day (max. 300 mg/day), canakinumab max. 300 mg every 4 weeks, tocilizumab (for body weight > 30 kg) 8 mg/kg (max. 800 mg) i.v. every 2 weeks and (for body weight < 30 kg) 12 mg/kg every 2 weeks. In addition, non-steroidal anti-inflammatory drugs may be used for symptom relief throughout. Combination therapy with biologic agents is discouraged. Abbreviations: ANA, anakinra; CAN, canakinumab; CID, clinical inactive disease; GC, glucocorticoids; IVMP, intravenous methylprednisolone pulse; PDN, prednisone/prednisolone equivalent. *not addressed by these strategies. ↓ = decrease dose or frequency (taper); ↑ = increase dose or frequency

Fig. 3

Treat-to-target consensus treatment strategy for definitive SJIA. Maximal doses for glucocorticoids: i.v. methylprednisolone pulse therapy (20–30 mg/kg/day [max. 1000 mg/day) for 5 days or prednisolone equivalent 1–2 mg/kg/day (max. 80 mg/day). “Biologic” refers to anakinra, canakinumab or tocilizumab. Maximal doses for biologics: anakinra 8 mg/kg/day (max. 300 mg/days), canakinumab 8 mg/kg (max. 600 mg) every 4 weeks, tocilizumab (for body weight > 30 kg) 8 mg/kg (max. 800 mg) i.v. every 2 weeks and (for body weight < 30 kg) 12 mg/kg every 2 weeks. In addition, non-steroidal anti-inflammatory drugs may be used for symptom relief throughout. Abbreviations: ANA, anakinra; CAN, canakinumab; CID, clinical inactive disease; GC, glucocorticoids; i.a., intraarticular; IVMP, intravenous methylprednisolone pulse; MTX, methotrexate; NSAID, nonsteroidal anti-inflammatory drug; PDN, prednisone/prednisolone equivalent; TCZ, tocilizumab; TNF, tumor necrosis factor-alpha. ↓ = decrease dose or frequency (taper); ↑ = increase dose or frequency