Ciccia, F.

Cottone, M.

Macaluso, F.

Orlando, A.

Orlando, R.

Renna, S.

Rizzo, A.

ORLANDO, Ambrogio

ORLANDO, Rosalba

Ciccia, Francesco

RENNA, Sara

Rizzo, Aroldo

Cottone, Mario

MACALUSO, Fabio Salvatore

Archivio istituzionale della ricerca - Università di Palermo

Clinical beneﬁt of vedolizumab on articularmanifestations in patients with activespondyloarthritis associated with inﬂammatorybowel diseaseVedolizumab (VDZ) is a new biological agent which wasrecently approved for the treatment of inﬂammatory boweldisease (IBD)1 following the good clinical responses reported byclinical trials for both Crohn’s disease2 and ulcerative colitis.3However, the effects of VDZ on extraintestinal manifestationswere not reported in these trials, and the ‘real life’ experience isstill limited. On these premises, we read with interest the recentwork by Varkas et al4 reporting a series of ﬁve patients withIBD who were treated with VDZ and promptly developed newonset or exacerbation of spondyloarthritis (SpA), irrespective ofthe response to treatment on intestinal symptoms. Although thehypotheses proposed by the authors to explain such eventssound reasonable, we would like to report our different prelim-inary results on the effect of VDZ on IBD-associated SpA. FromJune to December 2016, a treatment with VDZ was started in53 patients. Data were collected prospectively. Patient character-istics and main results are shown in table 1. Notably, 81.1% ofpatients had been previously treated with at least one TNF-αinhibitor, and almost all (96.2%) were steroid dependent.Overall, 36 out of 53 patients (67.9%) completed the inductionphase at last observation, and the mean follow-up of the entirecohort was 2.6±1.6 months. Eight (15.1%) patients had ahistory of IBD-associated SpA but were inactive at the time ofinitiation of VDZ, whereas 14 (26.4%) had active SpA whenVDZ was started. First, no case of induction or ﬂare of arthritisand/or sacroiliitis was reported among the entire cohort, includ-ing the patients without a prior SpA diagnosis. Second, 6 out ofthe 14 patients with active SpA (46.2%)—all complaining ofperipheral arthropathy—experienced a sharp clinical beneﬁtafter the initiation of VDZ. About gut inﬂammation of these sixpatients, three of them were in clinical remission after 6 and12 weeks of therapy, two were in remission after 6 weeks (theyhave not reached week 12 yet) and one patient did not experi-ence any response on intestinal symptoms after 14 weeks oftreatment. As a consequence, our preliminary prospective dataindicate a potential beneﬁt of VDZ on IBD-associated SpA.Even if we do not reject the possibility that VDZ may inducenew onset or exacerbation of arthritis and/or sacroiliitis, the pre-vious demonstration of α4β7 in the joint5 6 and the recent evi-dence of the upregulation of mucosal vascular address in celladhesion molecule (MadCAM-1) in the high endothelial venulesof bone marrow in patients with active axial SpA7 seem tostrengthen the hypothesis of a beneﬁcial rather than a paradox-ical effect of α4β7 blockade on articular manifestations of IBD.Obviously, more details about the molecular mechanisms under-lying the α4β7 blockade in the joints are required, and largecohort studies are needed to provide more evidence on thesepreliminary ﬁndings.Ambrogio Orlando,1 Rosalba Orlando,1 Francesco Ciccia,2 Sara Renna,1Aroldo Rizzo,3 Mario Cottone,1 Fabio Salvatore Macaluso11Division of Internal Medicine, “Villa Soﬁa-Cervello” Hospital, Palermo, Italy2Di.Bi.M.I.S., Section of Rheumatology, University of Palermo, Palermo, Italy3Department of Pathology, “Villa Soﬁa-Cervello” Hospital, Palermo, ItalyCorrespondence to Dr Ambrogio Orlando, Division of Internal Medicine, “VillaSoﬁa-V. Cervello” Hospital, Palermo 90146, Italy; ambrogiorlando@gmail.comCompeting interests FSM: lecture grant from MSD. SR: served as an advisoryboard member for AbbVie and MSD, and received lecture grants from AbbVie, MSD,Takeda Pharmaceuticals, Zambon. AO: served as an advisory board member forAbbVie, MSD, Takeda Pharmaceuticals; received lecture grants from AbbVie, MSD,Takeda Pharmaceuticals, Sofar, Chiesi. MC: received ﬁnancial support for theorganisation of a second-level master degree in inﬂammatory bowel disease fromAbbVie, MSD, Takeda Pharmaceuticals and Sofar.Provenance and peer review Not commissioned; internally peer reviewed.Table 1 Characteristics of patients and main resultsVariable n=53Age (years), mean±SD 51.5±15.7Male gender, n (%) 28 (52.8)Smokers, n (%)Never 50 (94.3)Current 2 (3.8)Ex 1 (1.9)Type of disease, n (%)Crohn’s disease 34 (64.2)Ulcerative colitis 19 (35.8)Duration of disease (years), mean±SD 13.6±9.4Localisation of the disease, n (%)Crohn’s diseaseIleal 3 (8.8)Ileocolic 26 (76.5)Colic 4 (11.8)Upper gastrointestinal tract* 1 (2.9)Perianal disease 7 (20.6)Ulcerative colitisProctitis 0 (0.0)Left-sided 6 (31.6)Extensive 13 (68.4)Behaviour (Crohn’s disease), n (%)Inflammatory 16 (47.1)Stricturing 17 (50.0)Fistulising 1 (2.9)Previous resections (Crohn’s disease), n (%) 21 (61.8)Previous biological treatmentsYes 43 (81.1)No (naïve to biologics) 10 (18.9)Steroid-dependent, n (%) 51 (96.2)IBD-associated SpANo history 31 (58.5)History (inactive at initiation of VDZ) 8 (15.1)Active at initiation of VDZ 14 (26.4)Peripheral arthropathy 12 (85.7)Axial and peripheral arthropathy 2 (14.3)Clinical benefit on SpA following initiation of VDZ (n=14)No clinical benefit 8/14 (57.1)Improvement 6/14 (42.9)New onset/exacerbation of SpA induced by VDZ 0*In addition to an ileocolic localisation.IBD, inflammatory bowel disease; SpA, spondyloarthritis; VDZ, vedolizumab.  1 of 2Ann Rheum Dis September 2017 Vol 76 No 9Correspondencegroup.bmj.com on November 16, 2017 - Published by http://ard.bmj.com/Downloaded from REFERENCES1 Armuzzi A, Gionchetti P, Daperno M, et al. Expert consensus paper on the use ofVedolizumab for the management of patients with moderate-to-severe InﬂammatoryBowel Disease. Dig Liver Dis 2016;48:360–70.2 Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction andmaintenance therapy for Crohn’s disease. N Engl J Med 2013;369:711–21.3 Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenancetherapy for ulcerative colitis. N Engl J Med 2013;369:699–710.4 Varkas G, Thevissen K, De Brabanter G, et al. An induction or ﬂare of arthritis and/orsacroiliitis by vedolizumab in inﬂammatory bowel disease: a case series. Ann RheumDis5 Salmi M, Jalkanen S. Endothelial ligands and homing of mucosal leukocytesin extraintestinal manifestations of IBD. Inﬂamm Bowel Dis 1998;4:149–56.6 Salmi M, Jalkanen S. Human leukocyte subpopulations from inﬂamed gut bind tojoint vasculature using distinct sets of adhesion molecules. J Immunol2001;166:4650–7.7 Ciccia F, Guggino G, Rizzo A, et al. Type 3 innate lymphoid cells producingIL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial ﬂuidand bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis2015;74:1739–47.2 of 2 Ann Rheum Dis September 2017 Vol 76 No 9To cite Orlando A, Orlando R, Ciccia F, et al. Ann Rheum Dis 2017;76:e31.Ann Rheum Dis 2017;76:e31. doi:10.1136/annrheumdis-2016-211011CorrespondenceReceived 21 December 2016Revised 27 December 2016Accepted 28 December 2016Published Online First 17 January 2017► http://dx.doi.org/10.1136/annrheumdis-2016-2100452017;76:878–81.group.bmj.com on November 16, 2017 - Published by http://ard.bmj.com/Downloaded from inflammatory bowel diseasespondyloarthritis associated withmanifestations in patients with active Clinical benefit of vedolizumab on articularAroldo Rizzo, Mario Cottone and Fabio Salvatore MacalusoAmbrogio Orlando, Rosalba Orlando, Francesco Ciccia, Sara Renna,doi: 10.1136/annrheumdis-2016-21101120172017 76: e31 originally published online January 17,Ann Rheum Dis  http://ard.bmj.com/content/76/9/e31Updated information and services can be found at: These include:References #BIBLhttp://ard.bmj.com/content/76/9/e31This article cites 6 articles, 2 of which you can access for free at: serviceEmail alertingbox at the top right corner of the online article. Receive free email alerts when new articles cite this article. Sign up in theNoteshttp://group.bmj.com/group/rights-licensing/permissionsTo request permissions go to:http://journals.bmj.com/cgi/reprintformTo order reprints go to:http://group.bmj.com/subscribe/To subscribe to BMJ go to:group.bmj.com on November 16, 2017 - Published by http://ard.bmj.com/Downloaded from 

Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease

Ambrogio Orlando

Rosalba Orlando

Francesco Ciccia

Sara Renna

Aroldo Rizzo

Mario Cottone

Fabio Salvatore Macaluso

Crossref

Annals of the Rheumatic Diseases

Orlando, Ambrogio

Renna, Sara

Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli"

https://iris.unipa.it/bitstream/10447/245706/1/e31.full.pdf

Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease

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Archivio istituzionale della ricerca - Università di Palermo

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Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli"