INTRODUCTION
Immunomodulatory therapies for psoriasis may predispose
patients to an increased risk of new infections or reactivation
of latent infections, such as tuberculosis,1,2 herpes zoster,3,4
and viral hepatitis.5,6 Because patients with active and chronic
infections are typically excluded from clinical studies, little is
known about the epidemiology and pathophysiology of hepatitis
infections in patients with psoriasis who are receiving biologic
therapies. Two recent studies in Taiwan, where the hepatitis B virus
(HBV) is endemic, reported a higher prevalence of HBV infection
in patients with psoriasis than in the general population.7,8
While the cytokine biology of HBV in patients with psoriasis is
not completely understood, cytokines involved in psoriasis may
be implicated in the pathophysiology of viral hepatitis.9 Tumor
necrosis factor α (TNF-α) and interleukin (IL)-12 can modulate the
clearance and control of HBV by suppressing viral replication.10,11
Therefore, patients treated with anti-TNF or anti-IL-12 therapies
may be at increased risk of new or reactivated HBV infections.
Cases of HBV reactivation have been reported in anti-TNF-treated patients with concurrent chronic HBV and inflammatory
diseases.5,10,12-16 Ustekinumab treatment in a patient with psoriasis
with chronic HBV was recently reported; no HBV reactivation
was observed.17 There are currently no reported cases of acute
HBV infection associated with anti-IL-12/23 therapy.
Ustekinumab (Stelara®; Janssen Biotech, Inc, Horsham, PA) is
a human, anti-IL-12/23 monoclonal antibody approved for the
treatment of moderate to severe psoriasis. The efficacy and
safety of ustekinumab has been demonstrated in more than
4,000 patients,18-28 with up to 5 years of follow-up.25 Here we
describe the first known reports of acute HBV infections in 2
ustekinumab-treated patients from 2 clinical trials.19,26
Case #1
Patient #1 was a 33-year-old white man from the phase 3 PHOENIX
1 study,19 with a 12-year history of moderate to severe psoriasis
and an otherwise uncomplicated medical history. At baseline, the
patient's disease was severe, with 77% body surface area involvement
and a Psoriasis Area and Severity Index (PASI) score of 46.
Prior treatments included topical steroids, ultraviolet B, psoralen
plus ultraviolet A, and acitretin. The patient had an HBV risk factor
of a same-sex relationship.27 Because infection history was selfreported,
blood samples collected at baseline were retrospectively
analyzed and were negative for HBV viral DNA.
The patient received ustekinumab 90 mg in March 2006 (week
0), with 2 induction doses 4 weeks apart, followed by maintenance
dosing every 12 weeks. By week 8, total clearance of
psoriasis was achieved, with 100% improvement from baseline
in PASI score (PASI 100). No adverse events were reported, and
liver enzyme levels were within normal limits through week 16.
At week 20 (36 days following the last dose), significant, transient
elevations in alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) were reported (Figure 1). Alkaline phosphatase
and total bilirubin levels were also elevated 1 to 2 weeks
later. Liver synthetic function, as assessed by serum albumin,
