Vedolizumab response in inflammatory bowel disease. Two years of follow-up

1130-0108/2020/112/7/555-558 • REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS © Copy igh 2020. SEPD y © ARÁN EDICIONES, S.L. REV ESP ENFERM DIG 2020:112(7):555-558 DOI: 10.17235/ eed.2020.7130/2020 Del Pino Bellido P, Bel is Jiménez M, Cas o La ia L, Maldonado Pé ez B, Sáez Díaz A, Caunedo Ál a ez A, A güelles-A ias F. Vedolizumab esponse in in lamma o y bowel disease. Two yea s o ollow-up. Re Esp En e m Dig 2020;112(7):555-558 DOI: 10.17235/ eed.2020.7130/2020 Vedolizumab esponse in in lamma o y bowel disease. Two yea s o ollow-up ORIGINAL PAPERS Pila del Pino Bellido1, Ma ía Bel is Jiménez1, Luisa Cas o La ia1, Belén Maldonado Pé ez1, An onia Sáez Díaz1, Ángel Caunedo Ál a ez1 and Fede ico A güelles-A ias1,2 1Gas oen e ology and Hepa ology Depa men . Hospi al Uni e si a io Vi gen Maca ena. Se illa, Spain. 2Facul ad de Medicina. Uni e sidad de Se illa. Se illa, Spain Recei ed: 15/04/2020 · Accep ed: 04/06/2020 Co espondence: Pila del Pino Bellido. Gas oen e ology and Hepa ology Depa men . Hospi al Uni e si a io Vi gen Maca ena. C/ D . Fed iani, 3. 41009 Se illa, Spain. e-mail: [email p o ec ed] ABSTRACT Backg ound: edolizumab is an α4β7 in eg in an agonis . The aim o his s udy was o e alua e he clinical esponse and emission a es wi h edolizumab. Me hods: his was a e ospec i e s udy o in lamma o y bowel disease (IBD) pa ien s who ecei ed edolizumab be ween 2016 and 2019. Response and emission a es we e analyzed a h ee, six, 12, 18 and 24 mon hs a e induc ion. Resul s: i y- i e pa ien s we e included. Clinical emis- sion a es in CD and UC a h ee, six, 12, 18 and 24 mon hs we e 19.35 %, 26.67 %, 30.43 %, 30 %, 38.89 % and 29.17 %, 26.09 %, 19.05 %, 26.67 % and 20 %, espec i ely. Conclusions: edolizumab is e ec i e o induc ion and main enance o clinical emission, bo h in C ohn’s disease and ulce a i e coli is. Keywo ds: Vedolizumab. Response. Remission. INTRODUCTION Vedolizumab is a ully humanized monoclonal IgG-1 an i- body ha selec i ely inhibi s he in e ac ion be ween α4β7 in eg in and mucosal add essin cell adhesion molecule-1 (MAdCAM-1). The e o e p e en ing lymphocy e anslo- ca ion om he blood in o he in lamed gu issue, which esul s in a educ ion in local in lamma ion (1). In he GEMI- NI s udies, edolizumab p o ed o be e ec i e as an induc- ion and main enance he apy in mode a ely o se e ely ac i e ulce a i e coli is (UC) and C ohn’s disease (CD) (2,3). Immunogenici y o edolizumab appea s o be low (4) and i seems o ha e a a o able sa e y p o ile (5). The p ima y aim o his s udy was o explo e, acco ding o he clinical p ac ice, he esponse and emission a es o edolizumab in ou cen e a e 24 mon hs. The seconda y aim was o assess whe he he e we e any p edic o s o esponse o edolizumab. MATERIALS AND METHODS S udy design and pa ien popula ion A e ospec i e, single cen e , obse a ional s udy was pe - o med a he Hospi al Uni e si a io Vi gen Maca ena, Se ille, Spain. Adul pa ien s (≥ 18 yea s) wi h CD o UC ecei ing edolizumab ( i s line o a e p e ious biologic ailu e) be ween Janua y 1s 2016 and July 1s 2019 we e included. Inclusion c i e ia we e: 1. A con i med diagnosis o CD o UC. 2. Pa ien s who ecei ed a leas a comple ed induc ion egimen o in a enous (IV) edolizumab. The s anda d dosing egimen consis ed in induc ion (300 mg IV a ze o, wo and six weeks), ollowed by main enance (300 mg IV e e y eigh weeks). Ou comes and de ini ions Response and emission de ini ions we e based on he Ha - ey B adshaw index (HBI) and Mayo sco ing index (MSI). Clinical emission was conside ed when MSI was ≤ 2 and HBI was ≤ 4. Clinical esponse was de ined as a dec ease o a leas wo poin s in he HBI o MSI index om hei p e i- ous sco e. Clinical esponse and emission we e analyzed a h ee, six, 12, 18 and 24 mon hs. Da a collec ion Da a o pa ien s ea ed wi h edolizumab om Janua y 2016 o July 2019 we e collec ed. All pa ien s we e ollowed in ou in lamma o y bowel disease (IBD) uni du ing he s udy P. del Pino Bellido e al. REV ESP ENFERM DIG 2020:112(7):555-558 DOI: 10.17235/ eed.2020.7130/2020 556 pe iod. An anonymous da abase was c ea ed ha included demog aphic a iables, smoking s a us, disease du a ion, disease pheno ype, p e ious and concu en IBD ea men s a baseline and clinical measu es o disease ac i i y a edol- izumab induc ion and a mon hs h ee, six, 12, 18, 24. S a is ical analysis Baseline demog aphic cha ac e is ics we e analyzed wi h s anda d desc ip i e s a is ics. Fo he analysis o quan i a- i e a iables, he non-pa ame ic U Mann-Whi ney es was used o he compa ison o he g oups. S a is ical signi i- cance was conside ed when p < 0.05. The p opo ion o clin- ical esponde s o edolizumab was compa ed a each ime poin using he Pea son’s Chi‐squa ed es . Uni a ia e and mul i a iable logis ic eg ession analyses we e pe o med o e alua e p edic o s o clinical and objec i e emission a h ee, six, 12, 18 and 24 mon hs. Wi h ega d o he esponse and emission a e analysis, pa ien s who had ad e se e ec s and hose who had no ye comple ed ollow-up we e exclud- ed. The e o e, he analysis included pa ien s wi h ea men ailu e (including hose equi ing su ge y). RESULTS Baseline pa ien cha ac e is ics Fi y- i e pa ien s (31 CD, 24 UC) we e included in he s udy. Figu e 1 summa izes he pa ien lowcha o he s udy and demog aphics a e summa ized in able 1; 83.9 % (26/31) o he pa ien s wi h CD and 100 % o he pa ien s wi h CU had ecei ed an i-TNFα he apies p io o ini ia ing edol- izumab. Mos o he pa ien s had ecei ed wo di e en an i-TNFα he apies (46.2 % CD, 62.5 % UC). The main ea- son o he onse o edolizumab was he lack o esponse o p e ious ea men s (64.5 % CD, 95.8 % UC), ollowed by ad e se e ec s o p e ious he apy (19.4 % CD, 4.2 % CU). In addi ion, 12.9 % s a ed edolizumab as a i s line he apy due o concomi an diseases. Table 1. Baseline pa ien demog aphics C ohn’s disease (n = 31) Ulce a i e coli is (n = 24) Gende (n, %) Men Women 8 (25.8) 23 (74.2) 13 (54.2) 11 (45.8) Age (mean ± SD) 41.7 ± 12.9 41.4 ± 14.9 Smoking s a us (n, %) Smoke s Non smoke s Ex-smoke 9 (29) 17 (54.8) 5 (16.1) 1 (4.2) 21 (87.5) 2 (8.3) Mon eal (n, %) Age A1: 8 (25.8) A2: 16 (51.6) A3: 7 (22.6) Loca ion L1: 6 (19.4) L2: 12 (38.7) L3: 12 (38.7) L3+L4: 1 (3.2) E1: 5 (20.8) E2: 14 (58.3) E3: 5 (20.8) Beha io B1: 13 (41.9) B2: 10 (32.3) B3: 8 (25.8) S1: 7 (29.2) S2: 10 (41.7) S3: 7 (29.2) Basal Ha ey B adshaw index (mean ± SD) 7.81 ± 2.02 -- Basal Mayo sco ing index (mean ± SD) -- 6,42 ± 2.3 Pe ianal disease (n, %) 11 (35.5) 1 (4.2) Ex ain es inal mani es a ions (n, %) 17 (54.8) 8 (33.3) P e ious an i-TNF ea men In liximab Adalimumab IFX y ADA IFX, ADA and golimumab IFX, ADA and ce olizumab ADA and ce olizumab 26 (83.9) 1 (3.8) 6 (23.1) 12 (46.2) 1 (3.8) 5 (19.2) 1 (3.8) 24 (100) 5 (20.8) 1 (4.2) 15 (62.5) 3 (12.5) 0 (0) 0 (0) Concomi an ea men AZT MTX Co icos e oids 2 (6.5) 4 (12.9) 22 (71) 5 (20.8) 3 (12.5) 16 (66.7) Fig. 1. S udy lowcha . 55 pa ien s 3 mon hs 6 mon hs 12 mon hs 18 mon hs 24 mon hs 31 CD 24 UC 31 29 16 12 10 9 1 non- esponde 1 did no comple e ollow-up 1 su ge y 1 los ollow-up 1 non- esponde 3 non- esponde s 2 did no comple e ollow-up 1 non- esponde 5 did no comple e ollow-up 1 in ole ance 1 in ole ance 1 non- esponde 1 did no comple e ollow-up 1 in ole ance 1 non- esponde 2 did no comple e ollow-up 4 non- esponde s 6 did no comple e ollow up 1 dea h 1 ad e se e en 1 su ge y 23 21 16 9 Vedolizumab esponse in in lamma o y bowel disease. Two yea s o ollow-up REV ESP ENFERM DIG 2020:112(7):555-558 DOI: 10.17235/ eed.2020.7130/2020 557 Clinical esponse and emission Clinical esponse and emission a es o edolizumab he a- py in CD and UC a e summa ized in igu es 1 and 2. O e all, he e was a dec ease in he Ha ey-B adshaw and Mayo index alues compa ed o baseline a h ee, six, 12, 18 and 24 mon hs (p < 0.05), as well as a dec ease in C- eac i e p o- ein. Nine pa ien s (6 CD, 3 UC) equi ed a 4 h dose o edol- izumab a week 10. Nine pa ien s (29 %) wi h CD equi ed in ensi ica ion o edolizumab. P edic o s o clinical and objec i e emission wi h edolizumab In he mul i a ia e analysis, no ela ionship was obse ed wi h age, smoking, ype o disease o p e ious an i-TNF and highe esponse a es. A 12 mon hs, highe esponse and emission a es we e obse ed in emales (81.8 %, p = 0.039), while 87.5 % o pa ien s wi h CD ea ed wi h co icos e oids did no espond a six mon hs. Fig. 2. Clinical esponse and emission a es in CD. Fig. 3. Clinical esponse and emission a es in UC. P. del Pino Bellido e al. REV ESP ENFERM DIG 2020:112(7):555-558 DOI: 10.17235/ eed.2020.7130/2020 558 Sa e y p o ile o edolizumab Fi e pa ien s (3 CD, 2 CU) expe ienced an ad e se e en , ou equi ed suspension. One pa ien p esen ed abdomi- nal pain and omi ing, wo pa ien s (1 CD, 1 UC) had skin lesions and he emaining wo expe ienced headaches and join pain. One pa ien (CD) died du ing ollow-up due o a espi a o y ailu e, as a consequence o a neph o ic syn- d ome in he con ex o a seconda y amyloidosis. DISCUSSION Pi o al s udies ha e shown edolizumab o be e ec i e and sa e, bo h o induc ion and main enance in pa ien s wi h IBD (2,3). CD pa ien s ea ed wi h edolizumab p esen clin- ical emission a es o a ound 19 % a h ee mon hs, shown bo h in a eal-wo ld coho in Canada (6), a p ospec i e Ge man s udy (7) and he p esen s udy (19.35 %). In UC, clinical emission a es a h ee mon hs ange be ween 23 and 51 % (6-12). Speci ically, we epo a es o 29.17 % in ou s udy. The a iance may be due o di e en inclusion c i e ia and de ini ions o ac i e disease, emission and esponse, which may cause di e ences in he se e i y o he disease be ween each popula ion. Fo ins ance, Ko ze epo ed a clinical emission a e o 51 % in UC. This s udy included 54 % o UC pa ien s wi h a p e ious biologic ail- u e, compa ed o 100 % in ou s udy. A 12 mon hs, clinical emission a es o 30.43 % in CD we e obse ed in ou s udy. This a e is sligh ly highe han ha epo ed by Ko ze (6), bu somewha lowe han hose epo ed in he GEMINI ial (3) and VICTORY conso ium ial (12). The di e ences wi h he GEMINI ial may be due o he p opo ion o pa ien s who had ecei ed p io an i- TNF he apy, which was limi ed o 50 %. Lowe emission a es we e ound in UC pa ien s han ha epo ed in he li e a u e (2,6,13,14), bo h a 12 and 18 weeks. The la ge numbe o pa ien s in his s udy compa ed o ou s may explain his di e ence. Subg oup analyses o GEMINI 2 showed highe clinical emission a es in males, younge pa ien s and CD pa ien s wi h a sho e disease du a ion (5). Howe e , highe esponse and emission a es we e obse ed in emales only a 12 mon hs compa ed o males. Besides, p e ious s udies sugges ha p io ea men wi h co icos e oid is associa ed wi h a lack o clinical emission (11,15). This is consis en wi h ou esul s, as pa ien s wi h concomi an ea men wi h co icos e oids we e less likely o achie e clinical emission a six mon hs. Ou s udy has se e al limi a ions. Fi s ly, he numbe o pa ien s is educed. Secondly, i is a e ospec i e and sin- gle-cen e s udy. Howe e , p elimina y in o ma ion was ob ained ha may ac as a s a ing poin o u u e e alua- ions o he impac o edolizumab in IBD pa ien s. In conclusion, ea men wi h edolizumab is e ec i e o induc ion and main enance o clinical emission in pa ien s wi h IBD who ha e no esponded o o ole a ed an i-TNF ea men . REFERENCES 1. Sc ibano ML. Vedolizumab o in lamma o y bowel disease: om an- domized con olled ials o eal-li e e idence. Wo ld J Gas oen e ol 2018;24(23):2457-67. DOI: 10.3748/wjg. 24.i23.2457 2. Feagan BG, Ru gee s P, Sands BE, e al. Vedolizumab as induc ion and main enance he apy o ulce a i e coli is. N Engl J Med 2013;369(8):699- 710. DOI: 10.1056/NEJMoa1215734 3. Sandbo n WJ, Feagan BG, Ru gee s P, e al. 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