53evaluated at 2 and 6 weeks based on patient questionnaires and physician assessment.
At week two, there was improvement in 46% of the infliximab group versus 6% of
the placebo group. At that point, all non-responders were offered and accepted
open-label infliximab. Sixty-nine percent (20/29) showed improvement at 6 weeks,
with 21% (6/29) deemed in complete remission [ 33 ].
Retrospective studies show a more robust response, attributable in part to less
limited dosing strategies. In one early retrospective study of 13 patients with moder-
ate to severe PG treated with infliximab, 3 responded after induction dosing, the
remaining 10 had response with ongoing dosing, and all patients were able to stop
corticosteroids [ 34 ]. In a more recent study of 67 patients in Spain with PG (61.2%
with underlying Crohn’s and 37.3% with UC), 31 were given infliximab (24) or
adalimumab (7), with improvement of PG in 29 (93.5%) [ 35 ]. Furthermore, the
results show that infliximab and adalimumab were definitive (i.e., no subsequent
therapy was needed over the study period) 91.7% and 100% of the time, respec-
tively [ 35 ].
It is important to recognize that there are also reports of “paradoxical” PG devel-
oping during treatment with infliximab [ 36 – 38 ]. In two cases, therapy was transi-
tioned to cyclosporine or adalimumab with resolution of skin lesions [ 36 , 38 ]. In
another case of a patient with underlying RA, infliximab was transitioned to etaner-
cept but the lesions persisted until their treatment with minocycline [ 37 ]. These
cases suggest that paradoxical PG is not a class effect, but might instead be a mani-
festation of immune response to a particular biologic agent.
Erythema Nodosum
Erythema nodosum (EN) is a dermatologic condition consisting of subcutaneous,
tender, red nodules that occur most commonly on the shins [ 32 ]. EN has been
described in association with several systemic inflammatory conditions but,
among patients with IBD, EN is most commonly associated with Crohn’s [ 8 , 9 ].
Since the activity of EN typically parallels the activity of intestinal disease, first-
line therapy focuses on treatment of the underlying IBD. When the intestinal
disease responds, the EN typically remits as well [ 6 ]. However, successful treat-
ment of idiopathic (and non-IBD-associated) EN with adalimumab has been
reported [ 39 ]. In addition, as in PG, “paradoxical” EN has been reported with the
use of infliximab [ 40 ].
Primary Sclerosing Cholangitis
Despite early reports of infliximab leading to biochemical improvement of comor-
bid primary sclerosing cholangitis (PSC) in patients with UC, this has not been
borne out in subsequent work. A randomized double blind placebo-controlled trial
4 Anti-TNF Therapy for Treatment of Extraintestinal Manifestations of Inflammatory