Immune Response to Pneumococcus and Tetanus Toxoid in Patients With Moderate-to-Severe Psoriasis Following Long-Term Ustekinumab Use

October 2013 | Volume 12 | Issue 10 | Original Article | 1122 | Copyright © October 2013

Carrie Brodmerkel PhD,a Eric Wadman BA,a Richard G. Langley MD,b Kim A. Papp MD,c Marc Bourcier
MD,d Yves Poulin MD,e Vincent Ho MD,f Lyn Guenther MD,g Rod Kunynetz MD,h Simon Nigen MD,i
Ronald Vender MD,j Norman Wasel MD,k Ming-Chun Hsu PhD,a and Philippe Szapary MD MSCEa

aJanssen Research & Development, LLC, Spring House, PA
bDalhousie University, Division of Dermatology, Department of Medicine, Halifax, NS, Canada
cProbity Medical Research, Waterloo, ON, Canada
dDermatology Clinic, Moncton, NB, Canada
eCentre Dermatologique du Quebec Metropolitain, Quebec, QC, Canada
fUniversity of BRitish Columbia, Department of Dermatology and Skin Science, Vancouver, BC, Canada
gThe Guenther Dermatology Research Center, London, ON, Canada
hUltranova Skincare, Barrie, ON, Canada
iInnovaderm Recherches, Montréal, QC, Canada
jDermatrials Research, Hamilton, ON, Canada
kStratica Medical, Edmonton, AB, Canada

BACKGROUND: Little is known about the impact of long-term use of immunosuppressive agents on immune response.
OBJECTIVES: Assess the impact of continuous maintenance ustekinumab treatment on patients' ability to mount immune responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell-dependent) vaccines.
PATIENTS and METHODS: Ustekinumab-treated patients with moderate-to-severe psoriasis treated in the long-term extension of the Phase 3 PHOENIX 2 trial (n=60) were compared with control psoriasis patients not receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination and 4 weeks post-vaccination were assessed for antibody responses.
RESULTS: No differences in the ability of ustekinumab-treated patients to respond to pneumococcal or tetanus toxoid vaccinations were observed compared with controls. A ≥2-fold increase in antibody levels in ≥7 of 14 serotypes of the pneumococcal vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%) patients following vaccination. Ustekinumab-treated patients achieved a ≥4-fold increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid between ustekinumab-treated and control groups.
CONCLUSION: Long-term treatment (≥3 years) with ustekinumab does not compromise the immune response to T-cell-dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2013;12(10):1122-1129.


Ustekinumab (Stelara® Janssen Biotech, Inc., Horsham,PA), a human, monoclonal antibody that binds the shared p40 subunit of interleukin (IL)-12 and IL-23, is approved for the treatment of moderate-to-severe chronic plaque psoriasis. The efficacy and safety of ustekinumab have been evaluated in more than 3,000 patients, with long-term treatment through up to five years of follow-up.1-7 Biologics such as ustekinumab and tumor necrosis factor (TNF) inhibitors modulate the immune system to inhibit the inflammatory processes dysregulated in patients with psoriasis. This immunomodulation could potentially impact the immune response to common antigens and compromise the immune status of treated patients.8,9 The effect of these agents on the ability of treated patients to mount an adequate immune response to common antigens is of clinical importance due to increased risk of infection in these patients.10 This has been studied primarily in rheumatoid arthritis (RA) and psoriatic arthritis with background methotrexate use.11-16 Limited data are available in patients with psoriasis in whom biologics are typically used as monotherapy.17-19