Background Corticosteroids (CS) remain the mainstay of therapy for childhood-onset systemic lupus erythematosus (cSLE) although there are no widely accepted dosing strategies of oral (PO CS) or intravenous CS (IV CS). We aimed to (1) develop a standardized CS dosing regimen (SSR) and (2) achieve consensus for this SSR among pediatric rheumatology and nephrology providers treating cSLE complicated by lupus nephritis (LN).
Methods Consensus formation techniques were used. A Delphi questionnaire pertaining to CS use in cSLE was completed to inform formats of the Patient Profiles (PP, Step 1). Using data from 147 children with proliferative LN at 8 major cSLE treatment sites in North America PP were generated providing information about the course of LN and extra-renal cSLE (ER) at 2 subsequent visits (Step 2). PP were sent to 142 physicians (PP-raters) experienced in cSLE to adjudicate the course of ER and LN and propose the PO/IV CS dosages (Step 3). Using data from PP for which consensus was achieved, the SSR was developed (Step 4) and refined based on responses from another questionnaire and a focus group of experienced physicians (Step 5). The SSR was tested using a second type of PP that described ER and LN courses for 6 months from the time of biopsy (Step 6). Consensus was defined as agreement of the majority of PP-raters (Step 3, Step 6).
Results For Step 1 and Step 3, 103 physicians answered Delphi questions and filled 353 PP (response rate: 73%). Step 6 activities were completed by 18 physicians (13.4 years of average experience) who were asked to review 33 PP each. This resulted in 564 completed PP ratings, of which 437 (77.5%) and 460 (81.6%) ratings yielded consensus on POSSR-and IV SSR dosing, respectively. PO CS and/or IV CS dosages as per the SSR (SSR-dose) depend on patient weight, the course of ER activity measured by the ER-SLEDAI score (figure 1d), and the course of LN described by changes/status of 3 LN response variables (LN-RVs, figure 1a-c). The SSR mimics dosing customs agreed upon by the PP-raters. Table 1 summarizes the SSR with focus on 2 ER/LN settings (1:stable ER/various LN courses; 2:stable LN/various ER courses), with several permutation of the course of ER (much worse, mild-moderately worse, active stable/improved, inactive) and LN (flare, mild-moderately worse, active stable/improved/partial renal remission (PRR), complete renal remission (CRR)). Use of dosages of PO CS ≥ 40 mg are governed by the course of LN except in major ER flares with potential organ damage. The SSR adjusts PO CS dosages in at least monthly intervals. IV CS are used for worsening of ER or LN courses that fail to respond to increased oral CS of ≥ 40 mg up to 4 weeks. Small decreases of PO CS occur even with stable ER or stable LN activity. Achieving CRR leads to more pronounced reduction of PO CS (table 1). Beyond 6 months post kidney biopsy (maintenance therapy), the PO/IV CS dosage is informed by LN status (PRR, CRR), the course of LN and ER activity (table 1).
Conclusions SSR for the treatment of cSLE complicated by LN has been developed which simulates PO/IV CS use among treating physicians. The proposed SSR may be useful for clinical care and to regulate background CS use during clinical trials of new medication for cSLE.
Acknowledgments Presented on behalf of the LaUNCH Project Investigator and supported by PORTICO (P30AR076316).
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