The most frequent grade 3-4 adverse events included diarrhoea ( 64 [ 16 % ] of 393 patients in the ipilimumab group vs seven [ 2 % ] of 396 in the placebo group ) , fatigue ( 40 [ 11 % ] vs 35 [ 9 % ] ) , anaemia ( 40 [ 10 % ] vs 43 [ 11 % ] ) , and colitis ( 18 [ 5 % ] vs 0 ) .