0 5 Novel novel JJ 6 15 therapies therapy NNS 16 19 for for IN 20 32 inflammatory inflammatory JJ 33 38 bowel bowel NN 39 46 disease disease NN 46 47 . . . 49 56 Looking look VBG 57 61 back back RB 62 64 at at IN 65 74 successes success NNS 75 78 and and CC 79 87 failures failure NNS 88 90 in in IN 91 96 newer new JJR 97 107 approaches approach NNS 108 110 to to TO 111 119 treating treat VBG 120 123 IBD IBD NNP 123 124 , , , 125 127 it it PRP 128 130 is be VBZ 131 149 tempting–although tempting–although IN 150 155 still still RB 156 169 difficult–to difficult–to JJ 170 174 draw draw NN 175 186 conclusions conclusion NNS 187 192 about about IN 193 205 pathogenesis pathogenesis NN 205 206 . . . 207 211 When when WRB 212 213 a a DT 214 221 therapy therapy NN 222 228 proves prove VBZ 229 238 effective effective JJ 238 239 , , , 240 242 do do VBP 243 253 clinicians clinician NNS 254 259 truly truly RB 260 264 know know VBP 265 268 how how WRB 269 271 it it PRP 272 277 works work VBZ 277 278 ? ? . 279 283 Even even RB 284 288 with with IN 289 290 a a DT 291 298 therapy therapy NN 299 301 as as IN 302 310 specific specific JJ 311 313 as as IN 314 322 anti-TNF anti-tnf JJ 323 331 antibody antibody NN 331 332 , , , 333 335 it it PRP 336 338 is be VBZ 339 342 not not RB 343 348 clear clear JJ 349 351 if if IN 352 355 the the DT 356 363 benefit benefit NN 364 366 is be VBZ 367 379 attributable attributable JJ 380 382 to to TO 383 389 simple simple JJ 390 397 binding binding NN 398 401 and and CC 402 411 clearance clearance NN 412 414 of of IN 415 424 TNF-alpha TNF-alpha NNP 425 427 or or CC 428 430 to to TO 431 438 binding binding NN 439 441 on on IN 442 445 the the DT 446 450 cell cell NN 451 458 surface surface NN 459 462 and and CC 463 473 subsequent subsequent JJ 474 482 deletion deletion NN 483 485 of of IN 486 489 the the DT 490 499 activated activate VBN 500 510 macrophage macrophage NN 510 511 . . . 512 516 When when WRB 517 518 a a DT 519 523 drug drug NN 524 531 appears appear VBZ 532 534 to to TO 535 537 be be VB 538 542 less less RBR 543 552 effective effective JJ 553 557 than than IN 558 569 preclinical preclinical JJ 570 576 models model NNS 577 584 suggest suggest VBP 584 585 , , , 586 589 can can MD 590 598 failures failure NNS 599 601 in in IN 602 615 effectiveness effectiveness NN 616 620 from from IN 621 629 delivery delivery NN 630 632 or or CC 633 639 dosing dosing NN 640 642 be be VB 643 657 differentiated differentiate VBN 657 658 ? ? . 659 662 The the DT 663 676 disappointing disappointing JJ 677 684 results result NNS 685 687 of of IN 688 696 clinical clinical JJ 697 703 trials trial NNS 704 708 with with IN 709 718 IL-10–so IL-10–so NNP 719 721 at at IN 722 726 odds odd NNS 727 731 with with IN 732 735 the the DT 736 746 prediction prediction NN 747 749 of of IN 750 757 benefit benefit NN 758 762 from from IN 763 769 animal animal NN 770 783 models–bring models–bring NN 784 788 into into IN 789 797 question question NN 798 801 the the DT 802 810 validity validity NN 811 813 of of IN 814 819 those those DT 820 826 models model NNS 827 829 as as RB 830 834 well well RB 835 837 as as IN 838 841 the the DT 842 851 soundness soundness NN 852 854 of of IN 855 861 design design NN 862 864 of of IN 865 868 the the DT 869 877 clinical clinical JJ 878 884 trials trial NNS 885 887 on on IN 888 893 which which WDT 894 902 efficacy efficacy NN 903 905 of of IN 906 911 IL-10 IL-10 NNP 912 914 is be VBZ 915 921 judged judge VBN 921 922 . . . 923 926 The the DT 927 938 variability variability NN 939 941 of of IN 942 950 response response NN 951 955 even even RB 956 958 to to TO 959 962 the the DT 963 967 most most RBS 968 976 narrowly narrowly RB 977 985 targeted target VBN 986 992 agents agent NNS 993 1001 suggests suggest VBZ 1002 1006 that that IN 1007 1012 these these DT 1013 1021 diseases disease NNS 1022 1025 are be VBP 1026 1029 far far RB 1030 1034 more more RBR 1035 1048 heterogeneous heterogeneous JJ 1049 1051 in in IN 1052 1058 humans human NNS 1059 1063 than than IN 1064 1066 in in IN 1067 1072 their their PRP$ 1073 1079 murine murine JJ 1080 1092 counterparts counterpart NNS 1092 1093 . . . 1094 1104 Clinicians Clinician NNPS 1105 1108 are be VBP 1109 1113 only only RB 1114 1118 just just RB 1119 1128 beginning begin VBG 1129 1131 to to TO 1132 1141 recognize recognize VB 1142 1153 subclinical subclinical JJ 1154 1161 markers marker NNS 1162 1164 of of IN 1165 1173 response response NN 1173 1174 , , , 1175 1178 and and CC 1179 1181 it it PRP 1182 1185 may may MD 1186 1190 soon soon RB 1191 1193 be be VB 1194 1202 possible possible JJ 1203 1205 to to TO 1206 1213 predict predict VB 1214 1222 response response NN 1223 1225 on on IN 1226 1229 the the DT 1230 1235 basis basis NN 1236 1238 of of IN 1239 1246 genetic genetic JJ 1247 1258 composition composition NN 1258 1259 . . . 1260 1263 For for IN 1264 1267 the the DT 1268 1274 moment moment NN 1274 1275 , , , 1276 1283 however however RB 1283 1284 , , , 1285 1288 the the DT 1289 1294 field field NN 1295 1297 of of IN 1298 1314 pharmacogenetics pharmacogenetic NNS 1315 1317 is be VBZ 1318 1327 embryonic embryonic JJ 1327 1328 . . . 1329 1339 Challenges challenge NNS 1340 1342 in in IN 1343 1353 developing develop VBG 1354 1357 new new JJ 1358 1369 therapeutic therapeutic JJ 1370 1380 strategies strategy NNS 1381 1388 include include VBP 1389 1392 not not RB 1393 1397 only only RB 1398 1409 identifying identify VBG 1410 1415 novel novel JJ 1416 1422 agents agent NNS 1422 1423 , , , 1424 1427 but but CC 1428 1432 also also RB 1433 1442 improving improve VBG 1443 1446 the the DT 1447 1458 definitions definition NNS 1459 1461 of of IN 1462 1470 clinical clinical JJ 1471 1480 endpoints endpoint NNS 1481 1484 and and CC 1485 1493 defining define VBG 1494 1502 efficacy efficacy NN 1503 1505 at at IN 1506 1509 the the DT 1510 1518 biologic biologic JJ 1519 1524 level level NN 1524 1525 . . . 1526 1530 Only only RB 1531 1538 through through IN 1539 1549 considered consider VBN 1550 1560 evaluation evaluation NN 1561 1563 of of IN 1564 1572 clinical clinical JJ 1573 1581 evidence evidence NN 1582 1585 may may MD 1586 1596 clinicians clinician NNS 1597 1606 determine determine VB 1607 1612 which which WDT 1613 1622 therapies therapy NNS 1623 1629 should should MD 1630 1636 remain remain VB 1637 1646 novelties novelty NNS 1647 1650 and and CC 1651 1656 which which WDT 1657 1663 should should MD 1664 1670 become become VB 1671 1673 an an DT 1674 1682 accepted accept VBN 1683 1687 part part NN 1688 1690 of of IN 1691 1694 the the DT 1695 1708 armamentarium armamentarium NN 1708 1709 . . .