Secukinumab Immunogenicity in Patients with Psoriatic Arthritis and Ankylosing Spondylitis during a 52-Week Treatment Period

Atul A. Deodhar¹, Dafna D Gladman², Iain B. McInnes³, Vibeke Strand⁴, Mengyuan Ren⁵, Sebastian Spindeldreher⁶, Luminita Pricop⁷, Brian Porter⁷, Jorge Safi⁷, Abhijit Shete⁸ and Gerard Bruin⁶, ¹Oregon Health & Science University, Portland, OR, ²Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada, ³Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom, ⁴Division of Immunology/Rheumatology, Stanford University, Palo Alto, CA, ⁵Novartis Pharmaceuticals, Shanghai, China, ⁶Novartis Institutes for BioMedical Research, Basel, Switzerland, ⁷Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, East Hanover, NJ, ⁸Novartis Pharma AG, Basel, Switzerland, Basel, Switzerland

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adverse events, antibodies and interleukins (IL), Biologics, Safety issues

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Secukinumab, a fully human monoclonal IgG1 antibody (mAb) that selectively targets IL-17A, is efficacious for the treatment of psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). mAb therapies may be associated with immunogenicity and the production of anti-drug antibodies (ADAb) that may cause adverse events (AEs) and/or affect drug pharmacokinetics and clinical response. Secukinumab immunogenicity occurred in 0.4% of patients with plaque psoriasis and not associated with loss of efficacy or issues of clinical concern.¹ Here we report the immunogenicity of secukinumab in PsA and AS patients treated with secukinumab for up to 52 weeks (Wks).

Methods: Immunogenicity in patients with PsA (FUTURE 1–3 studies) and AS (MEASURE 1–4 studies) exposed to secukinumab was evaluated at baseline (BL) and Wks 16 (AS only), 24, and 52. ADAb were defined as a positive ADAb (ADAb⁺) signal in ≥1 post-secukinumab treatment sample in patients negative at BL. ADAb positive samples were analyzed for drug-neutralizing potential, immunogenicity-related AEs and ADAb impact on secukinumab pharmacokinetics and efficacy through Wk 52.

Results: Of 1414 treated PsA and 1163 treated AS patients with samples for immunogenicity evaluation, 5 (0.35%) and 8 (0.68%) developed ADAb, respectively, over 52-wks (Table). All but 1 ADAb⁺PsA patients were biologic-naïve; 2/5 PsA and 1/8 AS ADAb⁺ patients received concomitant methotrexate, and 2/8 AS ADAb⁺patients received concomitant sulfasalazine. Associations between ADAb and secukinumab dose, frequency or mode of administration were not observed. ADAb were neutralizing in only 1 patient (with PsA), and none were associated with any immunogenicity-related AE. All ADAb were associated with normal secukinumab pharmacokinetics and none were associated with loss of secukinumab efficacy over 52 wks (Table). In the pharmacokinetics samples from patients with PsA or AS at the time points that immunogenicity was measured, 96% had secukinumab serum concentration below the drug tolerance level of 53.8 μg/ml, confirming sufficient immunogenicity sensitivity during treatment with secukinumab.

Conclusion: Secukinumab treatment was associated with a low incidence of immunogenicity in PsA and AS patients, as shown by ADAb detection in only 0.35% PsA patients and 0.68% AS patients over 52 wks in a database of >2500 patients, which is consistent with the low incidence of immunogenicity (0.4%) seen with secukinumab in patients with plaque psoriasis.¹

References:

Reich et al, Br J Dermatol. 2017;176:752

Table. Overview of patients with ADAb¹

	Study	Secukinumab dose	Prior biologics	ADAbs (titer)/ Neut-Ab	Immunogenicity-related AE	Impact on efficacy²	Pharmacokinetics behavior³
PsA trials	F2306	PBO- 75 mg	0	Wk24 (no titer)/Y	N	None	Normal
	F2312	PBO-150 mg	0	Wk52 (2.99)/N	N	None	Normal
	F2318	150 mg	Infliximab	Wk52 (2.14)/N	N	None	Normal
		150 mg	0	Wk24 (1.00)/N	N	None	Normal
		150 mg	0	Wk52 (2.59)/N	N	None	Normal
AS trials	F2305	10mg/kg–150 mg	0	Wk52 (2.39)/N	N	None	Normal
		PBO-150 mg	0	Wk52 (10.61)/N	N	None	Normal
	F2310	PBO-75 mg	0	Wk52 (39.39)/N	N	None	Normal
	F2314	PBO-300 mg	0	Wk52 (1.02)/N	N	None	Normal
	F2320	150 mg	0	Wk16 (6.35)/N W52/(2.96)/N	N	None	Normal
		150 mg No Load	0	Wk16 (2.70)/N	N	None	Normal
		150 mg	0	Wk24/(2.80)/N	N	None	Normal
		PBO–150 mg	0	Wk52/(2.89)/N	N	None	Normal
Neut-Ab=neutralizing antibodies; N, No; PBO, placebo; Y, yes; Wk, week. ¹Only positive ADAb results at the respective study wk are shown; ²Impact on efficacy is defined as: PsA, failure to achieve >20% reduction, compared to baseline, in both tender and swollen joint counts; AS, failure to achieve ASAS20, after previously achieving such improvement for at least 2 consecutive visits prior to the first detection of ADAb; ³Normal PK: Concentrations in ADAb-positive patients within observed range for all patients without ADAb

Disclosure: A. A. Deodhar, AbbVie Inc., Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc., and UCB, 2,AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, 5; D. D. Gladman, Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, 2,Amgen, AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, 5; I. B. McInnes, Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 2,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 5,Abbvie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, 8; V. Strand, AbbVie, Amgen, BMS, Celgene, Celltrion, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Sandoz and UCB., 5,AbbVie, Amgen, BMS, Celgene, Celltrion, Genentech, Janssen, Merck, Novartis, Pfizer, Sandoz and UCB., 9; M. Ren, Novartis, 3; S. Spindeldreher, Novartis, 1,Novartis, 3; L. Pricop, Novartis, 1, 3; B. Porter, Novartis, 1, 3; J. Safi, Novartis, 1,Novartis, 3; A. Shete, Novartis, 1, 3; G. Bruin, Novartis, 1,Novartis, 3.

To cite this abstract in AMA style:

Deodhar AA, Gladman DD, McInnes IB, Strand V, Ren M, Spindeldreher S, Pricop L, Porter B, Safi J, Shete A, Bruin G. Secukinumab Immunogenicity in Patients with Psoriatic Arthritis and Ankylosing Spondylitis during a 52-Week Treatment Period [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/secukinumab-immunogenicity-in-patients-with-psoriatic-arthritis-and-ankylosing-spondylitis-during-a-52-week-treatment-period/. Accessed .

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