Background The ability to self-administer subcutaneous (SC) belimumab would enhance treatment options for patients with SLE.

Objectives The pharmacokinetics (PK) across the change in administration from monthly belimumab intravenous (IV; 10 mg/kg) to weekly self-administration of belimumab 200 mg SC was examined in patients with SLE.

Methods Study 200339 (NCT02124798) enrolled adults with SLE who had received at least three monthly belimumab 10 mg/kg IV doses plus standard care, or who completed the open-label continuation phase of a randomised, controlled trial of belimumab SC (prefilled syringe). The target period between the last IV dose and first SC dose was 1 to 4 weeks. Open-label belimumab 200 mg SC (1 mL) was self-administered weekly (thigh or abdomen) using an autoinjector under clinic observation at Weeks 1, 2, 4, 8 and at home at Weeks 3, 5, 6, 7. PK samples were collected prior to SC administration at Weeks 1, 2, 4 and 8.

Results 95 patients enrolled: 91 completed the study. All except two patients transitioned from belimumab IV administration. Overall, 94% (89/95) of patients successfully self-administered belimumab at Weeks 1 and 2. A total of 736 injections were attempted over the 8-week treatment period, and 720 (98%) were concluded to be successful. Median serum belimumab trough concentration at Week 8 was 113 μg/mL (Figure). Following the switch from IV to SC, steady-state trough belimumab levels were attained on average by Week 2 (Figure). Median % changes from Week 1 to Week 8 were -51%, -23%, 1% and -3% for subjects with investigator-reported IV to SC switching time intervals of ≤1.5 weeks, 1.5–2.5 weeks, 2.5–3.5 weeks and >3.5 weeks, respectively.

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Figure 1.

Median belimumab serum concentration. Dashed line: lower limit of quantification (0.1 μg/mL)

Conclusions Patients with SLE successfully self-administered belimumab SC using a novel autoinjector. With a protocol-specified 1–4-week interval between the last IV and the first SC administration, baseline (Week 1) belimumab concentrations were on average similar to their eventual steady-state concentration. Since bioequivalent exposures were previously demonstrated for belimumab SC administration with autoinjector and prefilled syringe¹, the pharmacokinetically stable transition from IV to SC administration demonstrated here, is also assumed to hold for belimumab SC administered with the prefilled syringe. The median Week 8 belimumab concentration of 113 μg/mL confirms that steady-state average concentrations over the dosing interval (CavgSS) for weekly belimumab 200 mg SC are similar to the CavgSS of 110 μg/mL for belimumab 10 mg/kg IV every 4 weeks². The appropriate dosing interval between IV to SC dosing appears to be 1–4 weeks to start SC treatment when exposure is close to SC steady-state levels.

1. Struemper, H., et al., Clin Pharm Drug Dev, 2015, doi: 10.1002/cpdd.219.

2. Struemper, H., Roth, D., Gordon, D. Arthritis Rheumatol 2014;66(Suppl 10): S292

Acknowledgement Study funded by GSK. Louisa Pettinger, PhD, Fishawack Indicia Ltd, UK, provided submission assistance funded by GSK.

Disclosure of Interest S. Sheikh: None declared, N. L. Fox Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, A. Hammer Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, H. Struemper Shareholder of: GlaxoSmithKline, Employee of: PAREXEL, J. Groark Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, D. Roth Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, D. Gordon Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline