A phase 2, 24-week, randomized, placebo-controlled, double-blind study examining the efficacy and safety of an anti-interleukin-12 and -23 monoclonal antibody in patients with relapsing-remitting or secondary progressive multiple sclerosis.
BACKGROUND
Interleukins 12 and 23 (IL-12/23) have been implicated in multiple sclerosis (MS) pathogenesis. This study assessed the efficacy and safety of ABT-874, a monoclonal anti-IL-12/23 antibody, in active relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS).


METHODS
In this 24-week study, patients with RRMS or SPMS received ABT-874 200 mg every other week (EOW), ABT-874 200 mg every week (EW), or placebo. The cumulative number of gadolinium-enhanced lesions, relapse rate, disability progression, and adverse events were measured.


RESULTS
215 patients were randomized (ABT-874 200 mg EOW, N = 76; ABT-874 200 mg EW, N = 70; placebo, N = 69). At week 24, gadolinium-enhanced lesions were statistically significantly reduced with ABT-874 200 mg EOW vs. placebo (mean number [SD]: 5.4 [8.1] vs. 7.6 [14.4], p = 0.003), but not with ABT-874 200 mg EW (6.8 [11.3], p = 0.134). Mean relapse rate (relapses/y) was significantly lower for ABT-874 200 mg EW vs. placebo (0.1 [95% CI -0.0, 0.3] vs. 0.5 [0.2, 0.8], p = 0.007). Changes from baseline in disability scores and incidences of adverse events were not significantly different across treatment groups, although a numerically greater percentage of serious adverse events was reported for ABT-874 treatment groups.


CONCLUSIONS
Although rates of adverse events were not significantly different between ABT-874 treatment groups and placebo, the magnitude of ABT-874 efficacy was less than that observed with other agents currently in development for MS treatment. Anti-IL-12/23 monotherapy does not appear to warrant further testing as monotherapy treatment for MS.
University of Colorado Health Sciences Center, Aurora, Colorado, USA. timothy.vollmer@uchsc.edu
Timothy L
TL
Vollmer
Daniel R
DR
Wynn
M Shamsul
MS
Alam
Joaquin
J
Valdes
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002170:Canada; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015990:Placebo Effect; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D018664:Interleukin-12; C544528:briakinumab