Infliximab, a chimeric monoclonal antibody, is currently approved for RA, Crohn's disease, PsA, AS, and ulcerative colitis. For PsA, it typically is administered as an intravenous infusion every 8 weeks. Two placebo-controlled trials in PsA have been conducted: the Infli-ximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT, n =104) (Antoni et al. 2005a) and a phase III study, IMPACT II (n = 200) (Antoni et al. 2005b). In both studies, the drug was administered 5 mg/kg intravenously and background DMARD use was allowed, but not required. In IMPACT II, MTX was the only DMARD allowed. In both studies, about half of enrolled patients received treatment with concomitant MTX. This did not have an impact on efficacy.
Within IMPACT, 69 % of inflimab patients and 8 % of placebo patients showed an ACR 20 response at 16 weeks (p <0.001), and 78% and 18% showed a PsARC response (p<0.001), respectively. Patients with a good or moderate European League Against Rheu-
PASI 75 Hc*|]otiw
Tolal Sharp Score
Fig. 10.4. Phase 3 Trial of Etanercept in PsA (Mease 2004)
Phase- 3 tri.il Etanercept in PsA.
Patients -205 randomized to etanercept. 25mg sc twice weekly vs. placebo.
Methotrexate, nonsteroidal and prednisone < 10mg allowed. Etanercept ■ Placebo □
a) Primary outcome: ACR20, Week 12: 59% patients on etanercept showed improvement vs 15% placebo. 104 placebo, 101 etanercept.
b) PAS! 75 ( Psoriatic Area and Skin Index), an assessment of skin, PASI 75 scores showed an improvement in Ihe etanercept group, al 24 weeks with 23% improvement VB 3% in placebo group (p=0.001). 62 placebo. 66 ctancrccpt.
c) Etanercept treated patients did not show progression ofTotal Sharp Score Week 48; Erosion Score, or Joint Spaee Narrowing Score, implying inhibition of progressive joint destruction compared to progressive changes in these scores in the non-etancrccpt group over one year.
matism (EULAR) response were 85 % and 23 %, respectively (p <0.001) (Antoni et al. 2005). Enthesitis and dactylitis improved significantly. Thirty-nine patients had a baseline PASI of 2.5. Of these, 67% had at least a PASI 75 response compared to 0.05% in the placebo group (p = 0.001). In an open-label, 1-year follow-up of this group, patients originally taking placebo quickly achieved similar results with equivalent efficacy (Antoni et al. 2005). Radiographic data of hands and feet (including the DIPs of the hands) were analyzed according to the modified van der Heijde-Sharp method. These showed no disease progression in both groups over 50 weeks. Due to the short duration of placebo treatment (14 weeks), no difference in the treatment groups could be shown over 1 year. However, the calculated annual progression rate was reduced, indicating that even delayed treatment with infliximab after 14 weeks inhibited radiographic progression of PsA (Antoni et al. 2004).
Results from IMPACT II showed an ACR 20 in 58% and 11% (p <0.001) (Fig. 10.5a), PsARC response in 77 % of infliximab patients and 27 % of placebo patients (p <0.001), and PASI 75 in 65% and 2%, respectively (p = 0.001) 14 weeks (Fig. 10.5b) (Antoni et al. 2005). Median PASI improvement in ACR 20 responders was 87%, and 74% in ACR 20 non-responders, suggesting that skin response could be achieved even when joint response was not demonstrated (Mease et al. 2004a). As in the etanercept trial, measures of physical function and quality of life showed significant improvement. Presence of dactylitis and enthesitis (palpation of
Achilles tendon and plantar fascia insertions) was assessed at baseline and at 6 months and showed significant improvement in the treatment group. Radiographic data showed no evidence of disease progression in infliximab patients as compared to progression noted in placebo patients at week 24 (van der Heidje et al. 2005). When PsA-specific radiographic features, including pencil-in-cup deformities and gross osteoly-sis, were examined, there was no difference between the treatment groups, a finding also found in radiographic results of the other anti-TNF-a agents.
Was this article helpful?