Response to Tetanus and Pneumococcal Vaccination Following Administration of Ixekizumab in Healthy Participants

Elisa V Gomez, Jessie L Bishop, Kimberley Jackson, Talia M Muram, Diane Phillips, Elisa V Gomez, Jessie L Bishop, Kimberley Jackson, Talia M Muram, Diane Phillips

Abstract

Background: Ixekizumab (IXE) is an interleukin (IL)-17A antagonist approved for the treatment of adults with moderate-to-severe psoriasis.

Objective: The objective of this study was to determine if the immune response to tetanus and pneumococcal vaccines in healthy subjects administered IXE was noninferior to control.

Methods: In a randomized, open-label, parallel-group study, adult subjects received vaccinations alone (N = 42, control) or in combination with 160 mg IXE subcutaneously 2 weeks prior to vaccination and 80 mg IXE on the day of vaccination (N = 41, IXE). Response to tetanus vaccination was defined as anti-tetanus antibodies ≥ 1.0 IU and a ≥ 1.5-fold increase if baseline was ≤ 1.0 IU or a ≥ 2.5-fold increase if baseline was > 1.0 IU. Response to pneumococcal vaccination was defined as a ≥ 2-fold increase from baseline in anti-pneumococcal antibodies against > 50% of the 23 serotypes. The primary outcomes were the percentages of patients with a response to the tetanus and pneumococcal vaccines 4 weeks after vaccination. A noninferiority analysis of IXE to control using a 40% margin was evaluated for the primary outcomes. Safety and pharmacokinetics were also assessed.

Results: IXE (38 completers) was noninferior to control (41 completers) based on the difference in the proportion of responders to tetanus [1.4%; 90% confidence interval (CI) - 16.6 to 19.2] and pneumococcal (- 0.8%; 90% CI - 12.9 to 11.0) vaccines. Twenty subjects (14 IXE, six control) reported 43 mild treatment-emergent adverse events.

Conclusion: IXE does not suppress the humoral immune response to non-live vaccines and was well tolerated in healthy subjects. ClinicalTrial.gov identifier: NCT02543918.

Conflict of interest statement

The authors are employees and stockholders of Eli Lilly and Company.

Figures

Fig. 1
Fig. 1
Study design (NCT02543918). *Vaccine antibody samples taken prior to IXE administration. AB antibody, IXE ixekizumab
Fig. 2
Fig. 2
Noninferiority plot [90% confidence interval (CI)] of the treatment difference of responders to the tetanus (Boostrix) and pneumococcal (Pneumovax 23) vaccines 4 weeks after vaccination (week 6). CIs for the difference in proportions between the two groups calculated using the Newcombe method based on the Wilson score. A responder to tetanus (Boostrix) vaccine is defined as having a post-vaccination anti-tetanus antibody (ATAb) level of ≥ 1 IU and a ≥ 1.5-fold increase (50% increase) from baseline if the baseline pre-vaccination level is ≤ 1.0 or a ≥ 2.5-fold increase (150% increase) from baseline if the pre-vaccination level is > 1.0 IU. A responder to the pneumococcal (Pneumovax 23) vaccine is defined as having a ≥ 2-fold increase (100% increase) from baseline in anti-pneumococcal antibody (APAb) levels against > 50% of the 23 serotypes

References

    1. Eli Lilly and Company. Taltz (ixekizumab) [prescribing information]. 2016. . Accessed 15 May 2017.
    1. Wine-Lee L, Keller SC, Wilck MB, Gluckman SJ, Van Voorhees AS. From the Medical Board of the National Psoriasis Foundation: vaccination in adult patients on systemic therapy for psoriasis. J Am Acad Dermatol. 2013;69:1003–1013. doi: 10.1016/j.jaad.2013.06.046.
    1. Rahier JF, Moutschen M, Van Gompel A, Van Ranst M, Louis E, Segaert S, et al. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford). 2010;49:1815–1827. doi: 10.1093/rheumatology/keq183.
    1. Williams WW, Lu PJ, O’Halloran A, Kim DK, Grohskopf LA, Pilishvili T, et al. Surveillance of vaccination coverage among adult populations-United States, 2014. MMWR Surveill Summ. 2016;65:1–36. doi: 10.15585/mmwr.ss6501a1.
    1. Tay L, Leon F, Vratsanos G, Raymond R, Corbo M. Vaccination response to tetanus toxoid and 23-velent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects. Arthritis Res Ther. 2007;9:R38. doi: 10.1186/ar2174.
    1. Bingham CO, 3rd, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled trial. Arthritis Rheumatol. 2010;62:64–74. doi: 10.1002/art.25034.
    1. Winthrop KL, Silverfield J, Racewicz A, Neal J, Lee EB, Hrycaj P, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016;75:687–695. doi: 10.1136/annrheumdis-2014-207191.
    1. Zhou H, Jang H, Fleischmann R, Bouman-Thio E, Xu Z, Marini JC, et al. Pharmacokinetic and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol. 2007;47:383–396. doi: 10.1177/0091270006298188.
    1. Brodmerkel C, Wadman E, Langley RG, Papp KA, Bourcier M, Poulin Y, et al. Immune response to pneumococcus and tetanus toxoid in patients with moderate-to-severe psoriasis following long-term ustekinumab use. J Drugs Dermatol. 2013;12:1122–1129.
    1. Chioato A, Noseda E, Stevens M, Gaitatzis N, Kleinschmidt A, Picaud H. Treatment with the interleukin-17A-blocking antibody secukinumab does not interfere with the efficacy of influenza and meningococcal vaccinations in healthy subjects: results of an open-label, parallel-group, randomized single-center study. Clin Vaccine Immunol. 2012;19:1597–1602. doi: 10.1128/CVI.00386-12.
    1. Center for Disease Control and Prevention. Adult immunization schedule. 2017. . Accessed 15 May 2017.
    1. GlaxoSmithKline Biologicals. Boostrix (tetanus toxoid, reduced diphtheria toxoid and acellular pertussus vaccine) [package insert]. 2016. . Accessed 15 May 2017.
    1. Merck & Co., Inc. Pneumovax 23 (pneumococcal vaccine polyvalent) [package insert]. 2015. . Accessed 15 May 2017.
    1. Daly TM, Pickering JW, Zhang X, Prince HE, Hill HR. Multilaboratory assessment of threshold versus fold-change algorithms for minimizing analytical variability in multiplexed pneumococcal IgG measurements. Clin Vaccine Immunol. 2014;21:982–988. doi: 10.1128/CVI.00235-14.
    1. Tipples GA, Hamkar R, Mohktari-Azad T, Gray M, Parkyn G, Head C, et al. Assessment of immunoglobulin M enzyme immunoassays for diagnosis of measles. J Clin Microbiol. 2003;41:4790–4792. doi: 10.1128/JCM.41.10.4790-4792.2003.
    1. Moe CL, Sair A, Lindesmith L, Estes MK, Jaykus LA. Diagnosis of Norwalk virus infection by indirect enzyme immunoassay detection of salivary antibodies to recombinant Norwalk virus antigen. Clin Diagn Lab Immunol. 2004;11:1028–1034.
    1. Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998;17:873–890. doi: 10.1002/(SICI)1097-0258(19980430)17:8<873::AID-SIM779>;2-I.
    1. Fagerland MW, Lydersen S, Laake P. Recommended confidence intervals for two independent binomial proportions. Stat Methods Med Res. 2015;24:224–254. doi: 10.1177/0962280211415469.
    1. Agresti A, Coull BA. Approximate is better than ‘exact’ for interval estimation of binomial proportions. Am Stat. 1998;52:119–126.
    1. Mease PJ, Ritchlin CT, Martin RW, Gottlieb AB, Baumgartner SW, Burge DJ, et al. Pneumococcal vaccine response in psoriatic arthritis patients during treatment with etanercept. J Rheumatol. 2004;31:1356–1361.
    1. Visvanathan S, Keenan GF, Baker DG, Levinson AI, Wagner CI. Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate plus methotrexate or methotrexate alone. J Rheumatol. 2007;34:952–957.
    1. Kaine JL, Kivitz AJ, Birbara C, Luo AY. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol. 2007;34:272–279.
    1. World Health Organization. Annex 5. Recommendations to assure the quality, safety, and efficacy of tetanus vaccines (adsorbed). 2017. . Accessed 15 May 2017.
    1. Paris K, Sorensen RU. Assessment and clinical interpretation of polysaccharide antibody responses. Ann Allergy Asthma Immunol. 2007;99:462–464. doi: 10.1016/S1081-1206(10)60572-8.
    1. Daly TM, Hill HR. Use and clinical interpretation of pneumococcal antibody measurements in the evaluation of humoral immune function. Clin Vaccine Immunol. 2015;22:148–152. doi: 10.1128/CVI.00735-14.
    1. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345–356. doi: 10.1056/NEJMoa1512711.
    1. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or control in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomized trials. Lancet. 2015;386:541–551. doi: 10.1016/S0140-6736(15)60125-8.
    1. Brown G, Malakouti M, Wang E, Koo JY, Levin E. Anti-IL-17 phase II data for psoriasis: a review. J Dermatol Treat. 2015;26:32–36. doi: 10.3109/09546634.2013.878448.
    1. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318–1328. doi: 10.1056/NEJMoa1503824.
    1. van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(83–98):e4.
    1. Callis Duffin K, Bagel J, Bukhalo M, Mercado Clement IJ, Choi SL, Zhao F, et al. Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A) J Eur Acad Dermatol Venereol. 2017;31:107–113. doi: 10.1111/jdv.13768.
    1. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2017;58:826–850. doi: 10.1016/j.jaad.2008.02.039.
    1. Whaley MJ, Rose C, Martinez J, Laher G, Sammons DL, Smith JP, et al. Interlaboratory comparison of the three multiplexed bead-based immunoassays for measuring serum antibodies to pneumococcal polysaccharides. Clin Vaccine Immunol. 2010;17:862–869. doi: 10.1128/CVI.00022-10.
    1. Zhang X, Simmerman K, Yen-Lieberman B, Daly TM. Impact of analytical variability on clinical interpretation of multiplex pneumococcal serology assays. Clin Vaccine Immunol. 2013;20:957–961. doi: 10.1128/CVI.00223-13.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel