Elewaut, Dirk

Van den Bosch, Filip

Varkas, Gaëlle

G Varkas

F Van den Bosch

D Elewaut

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Annals of the Rheumatic Diseases

Response to: ‘Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease’ by Orlando <i>et al</i>

Ghent University Academic Bibliography

Response to: ‘Clinical beneﬁt of vedolizumabon articular manifestations in patients withactive spondyloarthritis associated withinﬂammatory bowel disease’ by Orlando et alWe thank Orlando et al1 for the critical appraisal of our paper.2However, we believe that the limited sample size and the lack ofsufﬁcient follow-up do not support unmistakable evidence ofclinical beneﬁt of vedolizumab in spondyloarthritis (SpA). Firstof all, merely 36 out of 53 patients with inﬂammatory boweldisease (IBD) completed the 6-week induction phase at the lastrecorded observation, which makes the interpretation of datapremature. Hence, as stated in our paper, mean time to ﬂare inour patients was calculated at 64 days after the initiation ofvedolizumab, ranging up to 114 days in these selected cases.The patients presented in the series from Orlando et al are alsomuch older (mean 51.5 years vs 36.0 years) and display a higherrate of surgical intervention (>60%) compared with our cases,which may respectively reﬂect a population less likely todevelop SpA features and a disturbed gastrointestinal architec-ture in therapy-resistant patients. Similarly, no data on concomi-tant medication, which might be synergistic, are provided.Nevertheless, no induction or ﬂare of SpA was seen in this smallprospective cohort. This observation does not necessarilycontradict with our case series, as the prevalence of these ﬁnd-ings in clinical practice is currently unknown and should befurther investigated.Orlando et al do not report any induction or ﬂare of SpA intheir small prospective cohort, but go as far as suggesting aclinical beneﬁt. However, less than half of patients of 14 activepatients with SpA experienced a response, which was vaguelydescribed as a ‘sharp clinical beneﬁt’ at the level of the joint.Unfortunately, objective signs of disease activity and/or outcomemeasures such as MRI inﬂammation or imaging are lacking inthe report, making the data difﬁcult to interpret. Surprisingly,one of these six patients even responded well at the level of thejoint, in absence of a gut response. Although we cannot excludesome efﬁcacy, taking the high placebo response in SpA in up to20%,3 4 the follow-up time and the small sample size of thiscohort into account, precaution is needed to make ﬁrm conclu-sions based on these results. In any case, the efﬁcacy of vedoli-zumab in IBD-associated joint disease, if any, does not seem tomeasure up to the efﬁcacy of anti-tumour necrosis factorreported previously in over 60% in IBD-related arthritis.5 6 Thelack of mucosal vascular addressin cell adhesion molecule 1(MADCAM-1) expression in synovial tissue despite the presenceof α4β7 on synovial T cells in SpA, which contrasts with the gut-speciﬁc interaction with MADCAM-1, provides scientiﬁc ration-ale for a differential response on joint versus gut symptoms.7 8In conclusion, the overall efﬁcacy of vedolizumab inIBD-associated SpA remains unclear. The report of Orlandoet al suggests some level of response in selected cases but theseries is not sufﬁciently powered and the follow-up is too shortin duration to permit ﬁrm conclusions on efﬁcacy in SpA. It isclear that only placebo-controlled trials—and not cohort studies—will be able to address the remaining questions regarding theimpact of vedolizumab in IBD-associated SpA.G Varkas,1,2 F Van den Bosch,1,2 D Elewaut1,21Department of Rheumatology, Ghent University Hospital, Ghent, Belgium2VIB Inﬂammation Research Centre, Ghent University, Ghent, BelgiumCorrespondence to Dr D Elewaut, Department of Rheumatology, Ghent UniversityHospital, Ghent 9000, Belgium; dirk.elewaut@ugent.beContributors GV, FVdB and DE: study concept and design, analysis andinterpretation of data, manuscript preparation and manuscript revision.Competing interests None declared.Patient consent Obtained.Provenance and peer review Commissioned; internally peer reviewed.▸ http://dx.doi.org/10.1136/annrheumdis-2016-211011REFERENCES1 Orlando A, Orlando R, Ciccia F, et al. Clinical beneﬁt of vedolizumab on articularmanifestations in patients with active spondyloarthritis associated with inﬂammatorybowel disease. Ann rheum dis2 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 RheumDis3 Mease P, Sieper J, Van den Bosch F, et al. Randomized controlled trial ofadalimumab in patients with nonpsoriatic peripheral spondyloarthritis. ArthritisRheumatol 2015;67:914–23.4 Paramarta JE, De Rycke L, Heijda TF, et al. Efﬁcacy and safety of adalimumab for thetreatment of peripheral arthritis in spondyloarthritis patients without ankylosingspondylitis or psoriatic arthritis. Ann Rheum Dis 2013;72:1793–9.5 Van den Bosch F, Kruithof E, De Vos M, et al. Crohn’s disease associated withspondyloarthropathy: effect of TNF-alpha blockade with inﬂiximab on articularsymptoms. Lancet 2000;356:1821–2.6 Herfarth H, Obermeier F, Andus T, et al. Improvement of arthritis and arthralgia aftertreatment with inﬂiximab (Remicade) in a German prospective, open-label,multicenter trial in refractory Crohn’s disease. Am J Gastroenterol 2002;97:2688–90.7 Elewaut D, De Keyser F, Van Den Bosch F, et al. Enrichment of T cells carrying beta7integrins in inﬂamed synovial tissue from patients with early spondyloarthropathy,compared to rheumatoid arthritis. J Rheumatol 1998;25:1932–7.8 Salmi M, Rajala P, Jalkanen S. Homing of mucosal leukocytes to joints. Distinctendothelial ligands in synovium mediate leukocyte-subtype speciﬁc adhesion.J Clin Invest 1997;99:2165–72.  1 of 1Ann Rheum Dis September 2017 Vol 76 No 9To cite Varkas G, Van den Bosch F, Elewaut D. Ann Rheum Dis 2017;76:e32.Correspondence responseAnn Rheum Dis 2017;76:e32. doi:10.1136/annrheumdis-2016-211045Received 11 January 2017Accepted 16 January 2017Published Online First 9 February 20172017;76:e31.2017;76:878–81.group.bmj.com on March 14, 2018 - Published by http://ard.bmj.com/Downloaded from et alinflammatory bowel disease' by Orlando active spondyloarthritis associated withon articular manifestations in patients with Response to: 'Clinical benefit of vedolizumabG Varkas, F Van den Bosch and D Elewautdoi: 10.1136/annrheumdis-2016-2110452017 76: e32 originally published online February 9, 2017Ann Rheum Dis http://ard.bmj.com/content/76/9/e32Updated information and services can be found at: These include:References http://ard.bmj.com/content/76/9/e32#ref-list-1This article cites 6 articles, 1 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 March 14, 2018 - Published by http://ard.bmj.com/Downloaded from 

Response to: 'Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease' by Orlando et al

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Response to: 'Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease' by Orlando et al

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