Supplemental Digital Content 1. Details of the search strategy for each database included in this systematic review and meta-analysis
Database: Ovid MEDLINE(R) ALL <1946 to March 11, 2021>
Search Strategy:
---
1 exp inflammatory bowel diseases/ or colitis, ulcerative/ or crohn disease/ or Inflam$ Bowel$
Diseas$.ja,jn,jw. (84625)
2 ((colitis$ or enteritis$) adj2 granulomatous$).tw,kf. (592) 3 (ulcerative$ adj3 colitis$).mp. (50910)
4 (((enteritis$ or ileitis$ or ileitides$) adj3 regional$) or ileocolitis$).tw,kf. (2151) 5 ((inflammat$ adj2 bowel$ adj2 disease$) or (terminal$ adj2 ileitis$)).tw,kf. (53010) 6 (crohn$2 or crohn's).mp. (58464)
7 (nflammatory$ or bowel$ or ulcerative$ or colitis$ or crohn$2 or crohn's).tw,kf. and ibd.af.
(25565)
8 or/1-7 (118663)
9 Ustekinumab/ or (ustekinumab$ or Stelara$).mp. (2264)
10 Certolizumab Pegol/ or (certolizumab$ or cimzia$).tw,kw. or Infliximab/ or (infliximab$ or avakine$ or (antibody$ adj2 ca2 adj2 monoclonal$) or inflectra$ or remicade$ or remsima$ or revellex$).tw,kf. or Natalizumab/ or (antegren$ or natalizumab$ or tysabri$).tw,kf. (18767) 11 Adalimumab/ or (adalimumab$ or amjevita or cyltezo or d2e7-antibod$ or humira).mp.
(9049)
12 (vedolizumab or entyvio$ or (monoclonal$ adj3 antibod$ adj3 (idp02 or ldp-02 or mln02 or mln-02 or mln-0002 or mln0002))).tw,kf. (1054)
13 (golimumab or Simponi or CNTO 148 or CNTO-148).mp. (1351)
14 (tasocitinib$ or tofacitinib or cp690550 or cp-690550 or cp690 550 or cp-690 550 or xeljanz).mp. (1738)
15 (ozanimod or Zeposia or rpc1063 or rpc-1063).mp. (94)
16 (filgotinib or g-146034 or g146034 or glpg0634 or glpg-0634 or gs6034 or gs-6034).mp.
(125)
17 (mirikizumab or LY3074828 or LY-3074828).mp. (20)
18 (Risankizumab or abbv-066 or abbv066 or bi655066 or bi-655066 or risankizumab$ rzaa$
or skyrizi).mp. (164)
19 (guselkumab or Tremfya or cnto1959 or cnto-1959).mp. (300)
20 (briakinumab or abt874 or abt-874 or monoclonal$ antibod$ abt 874).mp. (74) 21 (MEDI2070 or brazikumab or amg-139 or amg139 or medi-2070 or medi2070).mp. (12) 22 (upadacitinib or abt494 or abt-494 or rinvoq).mp. (159)
23 (abrilumab or amg181 or amg-181 or medi-7183 or medi7183).mp. (14) 24 (etrolizumab$ or pro145223 or pro-145223or rhumab beta7).mp. (69) 25 Fingolimod Hydrochloride/ or (fingolimod$ or fty720 or fty-720 or gilenia or gilenya$).mp. (3586)
26 (apd-334 or apd334 or arginine or etrasimod$).mp. (125761) 27 or/9-26 (156014)
28 8 and 27 (9416)
29 limit 28 to (clinical trial, phase ii or clinical trial, phase iii) (125)
30 (phase 3 or phase3 or phase III or phaseIII or P3 or PIII).tw,kf. (71072) 31 (phase 2 or phase2 or phase II or phaseII or P2 or PII).tw,kf. /freq=3 (14790)
32 Clinical Trials, Phase II as Topic/ or Clinical Trials, Phase III as Topic/ or (Clinical Trial, Phase II or Clinical Trial, Phase III).pt. (66379)
33 (Trial$ adj3 ("1" or "2" or I or II)).tw,kf. (78708) 34 or/30-33 (186026)
35 28 and 34 (431)
36 limit 28 to "therapy (best balance of sensitivity and specificity)" (1112) 37 random$.tw. (1203625)
38 28 and 37 (834)
39 29 or 35 or 36 or 38 (1389)
40 39 not (exp Animals/ not (Human/ and exp Animals/)) (1382)
41 (animal$1 or mice or rat or rats or cat$1 or cattle$1 or dog$1 or goat$1 or horse$1 or rabbit$1 or sheep$1 or swine$1 or pig$1 or piglet* or canine$1 or feline$1 or porcine$ or calf or primate* or rodent$ or hamster$ or lamb$1 or monkey$1 or murine or veterinar*).ti. (2131989) 42 40 not 41 (1382)
43 limit 42 to english language (1315) 44 limit 43 to review (467)
45 43 not 44 (848)
46 meta analysis.mp,pt. or MEDLINE.tw. or systematic review.tw. (355438) 47 43 and 46 (267)
48 45 not 47 (732)
49 exp case-control studies/ or (case$ and control$).tw. or (case$ and series).tw. [Medline case series ] (1659588)
50 case reports/ or case report$.mp. (2252107) 51 48 not (50 not (49 and 50)) (722)
52 51 not case report.ti. [MEDLINE - Removing case Reports and retaining Case Series ] (722)
***************************
Database: Embase Classic+Embase <1947 to 2021 March 12>
Search Strategy:
---
1 exp *inflammatory bowel diseases/ or *colitis, ulcerative/ or *crohn disease/ (103426) 2 ((colitis$ or enteritis$) adj2 granulomatous$).tw,kw. (883)
3 (ulcerative$ adj3 colitis$).tw,kw. (72429)
4 (((enteritis$ or ileitis$ or ileitides$) adj3 regional$) or ileocolitis$).tw,kw. (2563) 5 ((inflammat$ adj2 bowel$ adj2 disease$) or (terminal$ adj2 ileitis$)).tw,kw. (90295) 6 (crohn$2 or crohn's).tw,kw. (88209)
7 ((nflammatory$ or bowel$ or ulcerative$ or colitis$ or crohn$2 or crohn's) and ibd).tw,kw.
(52085)
8 or/1-7 (181931)
9 *Ustekinumab/ or (ustekinumab$ or Stelara$).tw,kw. (5154)
10 *Certolizumab Pegol/ or (certolizumab$ or cimzia$).tw,kw. or Infliximab/ or (infliximab$ or avakine$ or (antibody$ adj2 ca2 adj2 monoclonal$) or inflectra$ or remicade$ or remsima$ or revellex$).tw,kw. or Natalizumab/ or (antegren$ or natalizumab$ or tysabri$).tw,kw. (65771) 11 *Adalimumab/ or (adalimumab$ or amjevita or cyltezo or d2e7-antibod$ or
humira).tw,kw. (23277)
12 (vedolizumab or entyvio$ or (monoclonal$ adj3 antibod$ adj3 (idp02 or ldp-02 or mln02 or mln-02 or mln-0002 or mln0002))).tw,kw. (3141)
13 *golimumab/ or (golimumab or Simponi or CNTO 148 or CNTO-148).tw,kw. (4709) 14 *tofacitinib/ or (tasocitinib$ or tofacitinib or cp690550 or cp-690550 or cp690 550 or cp- 690 550 or xeljanz).tw,kw. (4093)
15 *ozanimod/ or (ozanimod or Zeposia or rpc1063 or rpc-1063).tw,kw. (289)
16 *exp filgotinib/ or (filgotinib or g-146034 or g146034 or glpg0634 or glpg-0634 or gs6034 or gs-6034).tw,kw. (418)
17 *mirikizuma/ or (mirikizumab or LY3074828 or LY-3074828).tw,kw. (82)
18 *risankizumab/ or (Risankizumab or abbv-066 or abbv066 or bi655066 or bi-655066 or risankizumab$ rzaa$ or skyrizi).tw,kw. (322)
19 *guselkumab/ or (guselkumab or Tremfya or cnto1959 or cnto-1959).tw,kw. (621) 20 *briakinumab/ or (briakinumab or abt874 or abt-874 or monoclonal$ antibod$ abt 874).tw,kw. (335)
21 *brazikumab/ or (MEDI2070 or brazikumab or amg-139 or amg139 or medi-2070 or medi2070).tw,kw. (61)
22 *upadacitinib/ or (upadacitinib or abt494 or abt-494 or rinvoq).tw,kw. (514)
23 *abrilumab/ or (abrilumab or amg181 or amg-181 or medi-7183 or medi7183).tw,kw. (52)
24 *etrolizumab/ or (etrolizumab$ or pro145223 or pro-145223or rhumab beta7).tw,kw. (175) 25 *fingolimod/ or (fingolimod$ or fty720 or fty-720 or gilenia or gilenya$).tw,kw. (8517) 26 *etrasimod/ or (apd-334 or apd334 or arginine or etrasimod$).tw,kw. (117211)
27 or/9-26 (207972) 28 8 and 27 (26218)
29 limit 28 to (phase 2 clinical trial or phase 3 clinical trial) (753)
30 (phase 3 or phase3 or phase III or phaseIII or P3 or PIII).tw,kw. (131020) 31 (phase 2 or phase2 or phase II or phaseII or P2 or PII).tw,kw. /freq=3 (24554)
32 phase 3 clinical trial/ or "phase 3 clinical trial (topic)"/ or phase 2 clinical trial/ or "phase 2 clinical trial (topic)"/ (187662)
33 (Trial$ adj3 ("1" or "2" or I or II)).tw,kw. (138728) 34 or/30-33 (363326)
35 28 and 34 (1822)
36 29 or 35 [FIRST set focused on phase 2 phase 3 ] (1822) 37 randomized controlled trial/ or random$.tw. (1767798) 38 28 and 37 (2911)
39 38 and (remission/ or (remission$ or induct$ or survival or ((disease$ or event$ or progression$) adj2 free) or post-remission$ or postremission$).tw,kw.) (2010)
40 29 or 35 or 39 (3082)
41 40 not (Animal/ not (Human/ and Animal/)) (3082)
42 (animal$1 or mice or rat or rats or cat$1 or cattle$1 or dog$1 or goat$1 or horse$1 or rabbit$1 or sheep$1 or swine$1 or pig$1 or piglet* or canine$1 or feline$1 or porcine$ or calf or primate* or rodent$ or hamster$ or lamb$1 or monkey$1 or murine or veterinar*).ti. (2607443) 43 41 not 42 (3069)
44 limit 43 to english language (3029) 45 limit 44 to review (504)
46 44 not 45 (2525)
47 meta analysis/ or "systematic review"/ or systematic review.tw. (436316) 48 44 and 47 (388)
49 46 not 48 (2274)
50 exp case control study/ or (case$ and control$).tw. or (case$ and series).tw. [EMBASE case series ] (1126231)
51 case report/ or case report$.mp. (2784282) 52 49 not (51 not (50 and 51)) (2219)
53 52 not case report.ti. [EMBASE - Removing case Reports and retaining Case Series ] (2219)
Supplemental Digital Content 2. Rates of endoscopic improvement and remission
Supplemental Digital Content 3. Risk of bias assessment of included randomized control trials. + indicates low risk of bias, - indicates high risk of bias
Study
Random sequence generation
Allocation concealment
Blinding of participants
and personnel
Blinding out outcome
assessment
Complete outcome
data
Appropriate method of measuring outcome
Selective reporting
Overall risk of bias
CCX282-B phase 237 + + + + + + + Low
CCX282-B phase 325 + + + + + + + Low
Certolizumab phase 236 + + + + + + + Low
Certolizumab phase 3
(PRECISE 1)23 + + + + + + + Low
Certolizumab phase 324 + + + + + + + Low
CDP571 phase 238 + + + + + + + Low
CDP571 phase 326 + + + + + + + Low
Golimumab phase 2/348 + + + + + + + Low
Natalizumab phase 239 + + + + + + + Low
Natalizumab phase 3
(ENACT)27 + + + + + + + Low
Natalizumab phase 3
(ENCORE)28 + + + + + + + Low
Risankizumab phase 241 + + + + + + + Low
Risankizumab phase 3
(ADVANCE)21 + + + + + + + Low
Risankizumab phase 3
(MOTIVATE)21 + + + + + + + Low
Tofacitinib phase 243 + + + + + + + Low
Tofacitinib phase 329 + + + + + + + Low
Upadacitinib phase 2b42 + + + + + + + Low
Upadacitinib phase 330 + + + + + + + Low
Upadacitinib phase 331 + + + + + + + Low
Ustekinumab phase 235 + + + + + + + Low
Ustekinumab phase 322 + + + + + + + Low
Vedolizumab phase 240 + + + + + + + Low
Vedolizumab phase 332 + + + + + + + Low
Visilizumab phase 246 + - - - + + + High
Visilizumab phase 347 + + + + + + + Low
Ozanimod phase 244 + + + + + + + Low
Ozanimod phase 333 + + + + + + + Low
Etrolizumab phase 245 + + + + + + + Low Etrolizumab phase 3
(HIBISCUS 1)34 + + + + + + + Low
Etrolizumab phase 3
(HIBISCUS 2)34 + + + + + + + Low
