TY - JOUR
T1 - Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis
AU - Deodhar, Atul
AU - Gladman, Dafna D.
AU - McInnes, Iain B.
AU - Spindeldreher, Sebastian
AU - Martin, Ruvie
AU - Pricop, Luminita
AU - Porter, Brian
AU - Jorge, Safi
AU - Shete, Abhijit
AU - Bruin, Gerard
N1 - Publisher Copyright:
© 2020 Journal of Rheumatology. All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Objective. Secukinumab, a fully human antiinterleukin 17A monoclonal antibody, is efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). This study examined the immunogenicity of secukinumab in patients with PsA and AS exposed to secukinumab for up to 52 weeks. Methods. Antibody bridging assays were used to assess the immunogenicity of secukinumab in patients with PsA [FUTURE 1-3 studies, and AS (MEASURE 1-4 studies)]. Evaluations were at baseline and at weeks 16 (AS only), 24, and 52. Treatment-emergent antidrug antibodies (TE-ADA) were defined as a positive ADA signal in ≥ 1 posttreatment sample in patients negative at baseline. Positive samples were analyzed for drug-neutralizing potential, and effect of TE-ADA on secukinumab pharmacokinetics, immunogenicity-related adverse events (AE), and efficacy through Week 52 were assessed. Results. Of 1414 treated PsA and 1164 treated AS patients with samples available for immunogenicity evaluation, 5 (0.35%) and 8 (0.69%), respectively, developed TE-ADA. All but 1 PsA patient were biologic-naive; two of the 5 PsA and one of the 8 AS patients received concomitant methotrexate, and two of the 8 AS patients received concomitant sulfasalazine. Associations between TE-ADA and secukinumab dose, frequency, or administration mode were not observed. Other than one PsA patient, all TE-ADA were non-neutralizing. No TE-ADA were associated with any AE. All TE-ADA were associated with normal secukinumab pharmacokinetics and none were associated with loss of secukinumab efficacy. Conclusion. Secukinumab treatment was associated with a low (< 1%) incidence of immunogenicity in patients with PsA or AS. (clinicaltrials.gov: NCT01392326; NCT01752634; NCT01989468; NCT01358175; NCT01649375; NCT02008916; NCT02159053) (First Release November 15 2019; J Rheumatol 2020;47:539-47; doi:10.3899/jrheum.190116).
AB - Objective. Secukinumab, a fully human antiinterleukin 17A monoclonal antibody, is efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). This study examined the immunogenicity of secukinumab in patients with PsA and AS exposed to secukinumab for up to 52 weeks. Methods. Antibody bridging assays were used to assess the immunogenicity of secukinumab in patients with PsA [FUTURE 1-3 studies, and AS (MEASURE 1-4 studies)]. Evaluations were at baseline and at weeks 16 (AS only), 24, and 52. Treatment-emergent antidrug antibodies (TE-ADA) were defined as a positive ADA signal in ≥ 1 posttreatment sample in patients negative at baseline. Positive samples were analyzed for drug-neutralizing potential, and effect of TE-ADA on secukinumab pharmacokinetics, immunogenicity-related adverse events (AE), and efficacy through Week 52 were assessed. Results. Of 1414 treated PsA and 1164 treated AS patients with samples available for immunogenicity evaluation, 5 (0.35%) and 8 (0.69%), respectively, developed TE-ADA. All but 1 PsA patient were biologic-naive; two of the 5 PsA and one of the 8 AS patients received concomitant methotrexate, and two of the 8 AS patients received concomitant sulfasalazine. Associations between TE-ADA and secukinumab dose, frequency, or administration mode were not observed. Other than one PsA patient, all TE-ADA were non-neutralizing. No TE-ADA were associated with any AE. All TE-ADA were associated with normal secukinumab pharmacokinetics and none were associated with loss of secukinumab efficacy. Conclusion. Secukinumab treatment was associated with a low (< 1%) incidence of immunogenicity in patients with PsA or AS. (clinicaltrials.gov: NCT01392326; NCT01752634; NCT01989468; NCT01358175; NCT01649375; NCT02008916; NCT02159053) (First Release November 15 2019; J Rheumatol 2020;47:539-47; doi:10.3899/jrheum.190116).
KW - Ankylosing spondylitis
KW - Interleukin-17a
KW - Monoclonal antibody immunogenicity
KW - Psoriatic arthritis
KW - Secukinumab
UR - http://www.scopus.com/inward/record.url?scp=85077694137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077694137&partnerID=8YFLogxK
U2 - 10.3899/jrheum.190116
DO - 10.3899/jrheum.190116
M3 - Article
C2 - 31203228
AN - SCOPUS:85077694137
SN - 0315-162X
VL - 47
SP - 539
EP - 547
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 4
ER -