Early add-on use of belimumab as induction therapy for patients with childhood-onset systemic lupus erythematosus

Sir,

The efficacy and safety of belimumab, a human antibody inhibiting the biological activity of the B-cell activating factor, in the treatment of patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) has been reported.^1–4 Since glucocorticoid (GC) toxicity is a major concern in the treatment of SLE and LN, it is recommended that the use of GC be minimized and even withdrawn. ⁵ Thus, the add-on use of belimumab may be a viable option for the optimal management of SLE.^1–4 However, little data is available regarding the implications of the use of belimumab in a “real-world” setting for the treatment of childhood-onset SLE (cSLE).^6,7 In this context, we read with great interest a paper by Roberts et al. ⁷ in this journal. For the past 5 years, we have also used belimumab add-on treatment in nine patients with cSLE. Notably, three patients received belimumab as an add-on in an induction regimen comprising GC, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ). We found that belimumab was effective for successful and relatively rapid dose reduction of the concomitantly administered GC in these patients compared with patients who received the same induction regimen without belimumab.

Among nine patients with cSLE who received belimumab for at least 6 months in our hospital, we selected three patients who received early (within a month after initiation of induction therapy) intravenous belimumab (10 mg/kg every 2 weeks at initiation and every 4 weeks thereafter) as an add-on GC, MMF (1–1.5 g per day), and HCQ (200 mg per day) as induction therapy. To evaluate the efficacy of belimumab in these patients (Group A), we recruited three patients who received the same induction therapy without belimumab as historical controls (Group B). The clinical characteristics of the patients are shown in Table 1. All the patients met the classification criteria for SLE. Although four of the six patients had biopsy-proven LN, none had proliferative LN. The outcome measures, such as serum anti-dsDNA titers, urinary protein excretion/urinary creatinine ratio, and SLE disease activity index (SLEDAI), at baseline were relatively higher in Group A than in Group B. Decease in serum C3 level was also evident in Group A. After initiation induction therapy, sequential changes in these parameters equally improved in both groups (i.e., SLEDAI, median, in Group A and Group B were 2 v.s. 2 at 6 months of treatment, and 2 v.s. 1 at the observation point of 16 months, respectively); however, the dose reduction of concomitantly administered GC showed a tendency to be more rapid and smooth in Group A than in Group B at 6 months of treatments (median, 10 mg/day v.s. 12 mg/day, respectively) and persisted at the last observation point of a mean of 16 months (median, 4 mg/day v.s. 6.4 mg/day, respectively). No adverse reaction was observed with early add-on use of belimumab.

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Table 1.

Clinical characteristics of children with systemic lupus erythematosus who received induction therapy with belimumab (Group A) and without belimumab (Group B).

Variable	Group A (n = 3)	Group B (n = 3)
Age (years old), median (range)	13.7 (11.2–14.1)	12.1 (12–12.9)
Gender (girl/boy)	2, 1	3, 0
Serum creatinine (mg/dL), median (range)	0.37 (0.35–0.51)	0.45 (0.29–0.61)
Serum C3 level (mg/dL) (normal, 65–135 mg/dL), median (range)	52 (31–54)	70 (37–74)
Serum CH50 level (U/mL) (normal, 23.0–46.0 IU/mL), median (range)	13.1 (11.3–17.8)	16.4 (5–27.5)
Serum anti-dsDNA titer (IU/mL) (normal, <12.0 IU/mL), median (range)	≥380 (all showed ≥380)	8 (5.7–15.6)
U-prot./cre. (g/g creatinine), median (range)	0.44 (0.12–0.69)	0.11 (0.04–0.18)
Lupus nephritis classification, a median (range)	V/II/not obtained	II/II/not obtained
SLEDAI, median (range)	15 (12–19)	8 (6–15)
PDN dose (mg/day), median (range)	40 (40–60)	40 (15–60)

To date, early add-on use of belimumab as induction therapy in selected patients with SLE has rarely been reported. ⁸ Considering the mechanism of action of belimumab, we think that the early add-on use of the drug may be an attractive choice for managing patients with SLE in a real-world setting for long-term favorable outcomes, particularly in cSLE. In this context, we confirmed the successful and rapid dose reduction of concomitantly administered GC without flares in our patients possibly because of early belimumab add-on use. Thus, further studies on the early add-on use of belimumab in a larger number of patients with cSLE are warranted.