Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus

Abstract

Objective: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).

Methods: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic. The proportion able to self-administer at weeks 4 and 8 (clinic) and weeks 3, 5, 6, and 7 (home) were secondary endpoints. Belimumab PK, safety, and injection-site pain were assessed.

Results: 91/95 patients completed the study (withdrawals: adverse events (AEs): 3; lost to follow-up: 1). 93% were female, and mean (SD) age was 44.8 (12.50) years. The majority (99%, 89/90; no attempt, n = 5) successfully self-administered belimumab SC at weeks 1 and 2 (5 had clinic staff assistance), and 98% (85/87) successfully self-administered at weeks 4 and 8. Home-administration success rates were high (93%, (81/87) at weeks 3, 5, 6, and 7). Week 8 median trough concentration was 113 µg/mL. For patients with a ≤ 1.5-week interval between IV SC administration, week-1 concentrations were higher vs. week 8 (+ 51% median) but within a range observed with IV dosing; those with a ≥ 2.5-week interval had median differences close to 0. AEs and serious AEs were low, with no deaths; pain levels were low and decreased with subsequent injections.

Conclusion: Patients with SLE successfully self-administered belimumab SC using a novel autoinjector; the PK profile was stable following a switch from IV with acceptable AE and pain levels. The recommended dosing interval between IV to SC dosing is 1 - 4 weeks. .

Figure 1.. Study design. AE = adverse events; clinic = self-administration of belimumab SC at the clinic; home = self-administration of belimumab SC at home; IV = intravenous; PK = blood sample taken for pharmacokinetic analysis prior to belimumab administration; SC = subcutaneous.

Figure 2.. Autoinjector device. Registered design protection granted/pending. Image originally published in Struemper et al. 2015 [15].

Figure 3.. Patient disposition. ^aReceived ≥1 dose belimumab; ^bpatients included in the ITT population for whom ≥1 post belimumab treatment PK sample was analyzed. AE = adverse event; ITT = intent-to-treat; PK = pharmacokinetic.

Figure 4.. Percentage of successful injections at each week. Data missing for 5 patients at weeks 1 and 2, and for 8 patients at weeks 3 – 8. Data labels represent number of patients.

Figure 5.. Median belimumab serum concentration by week (PK population). Minimum and maximum values: week 1 (0, 504.29 µg/mL), week 2 (17.47, 467.86 µg/mL), week 4 (34.41, 278.27 µg/mL), week 8 (30.19, 296.47 µg/mL). Dashed line: lower limit of quantification (0.1 µg/mL). PK = pharmacokinetic.

Figure 6.. Effect of the IV-to-SC interval on week-8 to week-1 concentration difference (PK population^a). ^aExcludes two patients who received belimumab SC via prefilled syringe at study entry. Boxes represent the median, 25^th and 75^th percentiles. Ends of whiskers represent the maximum observation below the upper fence (75^th percentile + 1.5 × interquartile range) and the minimum observation above the lower fence (25^th percentile – 1.5 × interquartile range). Crosses (+) represent the mean. Circles with a cross (X) represent outliers. IV = intravenous; PK = pharmacokinetic; SC = subcutaneous.