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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 522-523

New-onset anterior uveitis in two patients on ustekinumab for inflammatory bowel disease


Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States

Date of Submission19-Oct-2020
Date of Acceptance13-Feb-2021
Date of Web Publication02-Jul-2021

Correspondence Address:
Dr. Kara C LaMattina
Department of Ophthalmology, Boston University School of Medicine, 85 East Concord Street, 8th Floor, Boston, MA 02118
United States
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_3248_20

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  Abstract 


This report presents the first published cases of new-onset uveitis in patients on ustekinumab therapy. We present two patients with inflammatory bowel disease who developed anterior uveitis while on ustekinumab 90 mg every 8 weeks. Both patients achieved quiescence of their uveitis and improved control of their systemic disease with increased dose frequency of ustekinumab at every 4 weeks. Further investigation is warranted to determine if a true association exists.

Keywords: Inflammatory bowel disease, ustekinumab, uveitis


How to cite this article:
Fridman G, LaMattina KC. New-onset anterior uveitis in two patients on ustekinumab for inflammatory bowel disease. Indian J Ophthalmol Case Rep 2021;1:522-3

How to cite this URL:
Fridman G, LaMattina KC. New-onset anterior uveitis in two patients on ustekinumab for inflammatory bowel disease. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 28];1:522-3. Available from: https://www.ijoreports.in/text.asp?2021/1/3/522/320092



Ustekinumab is the first-in-class, fully human immunoglobulin G1 kappa monoclonal antibody directed against interleukin (IL)-12 and IL-23.[1] It is presently under investigation for the treatment of uveitis in a clinical trial (NCT00771667). Thus far, its role in the management of uveitis has only been described in case reports. Several reports noted its beneficial use in patients with uveitis in the setting of psoriatic arthritis (PsA), Behcçet's disease and Crohn's disease (CD).[2],[3]

Adverse events reported for ustekinumab include mild infections and malaise.[1] In this study, we present two patients who developed new-onset inflammatory bowel disease (IBD)-associated uveitis while on ustekinumab for the treatment of systemic disease.


  Case Reports Top


Case 1

A 55-year-old woman presented complaining of difficulty reading. Her past medical history (PMH) included ulcerative colitis (UC) and CD (HLA-B27 negative), diagnosed at age 32, complicated by ileal perforation necessitating ileostomy, vulvar metastasis, bilateral avascular necrosis of the hip, and spondyloarthritis. Additional PMH included diabetes mellitus, hyperparathyroidism, and erythema nodosum. She failed or had limited response to multiple treatments, including mercaptopurine, infliximab, adalimumab, certolizumab, natalizumab, and methotrexate. She was subsequently started on ustekinumab 90 mg every 8 weeks which successfully controlled her systemic disease for 1.5 years prior to presentation.

On ophthalmologic exam, her best-corrected visual acuity (BCVA) was 20/25 in each eye and intraocular pressure (IOP) was 14 mmHg and 16 mmHg in the right and left eye, respectively. She was incidentally found to have bilateral 1+ keratic precipitates, 1+ anterior chamber cell, and 0.5+ flare. Her eye exam was otherwise normal. She was started on prednisolone acetate 1% four times daily. Upon follow up 5 weeks later her exam was quiescent, and she started a prednisolone taper. After consultation with her gastroenterologist, with consideration for how difficult her systemic disease control had been, the decision was made to escalate her current therapy of ustekinumab to every 4 weeks. She has not had any recurrent uveitic flares in nearly two years.

Case 2

A 26-year-old man presented complaining of bilateral eye pain and photophobia for 3 days about 2 months postinduction of ustekinumab. His PMH included UC (unknown HLA-B27 status) diagnosed at age 12 with resultant total colectomy; he was later diagnosed with CD and eosinophilic esophagitis. He underwent a treatment course with insufficient response to multiple biologics, including adalimumab, infliximab, and mercaptopurine, leading to dependence on oral budesonide, which he was taking daily for several years. Multiple attempts were made to taper off budesonide unsuccessfully. He was subsequently started on ustekinumab 90 mg every 8 weeks with a simultaneous slow budesonide taper.

On ophthalmologic exam his BCVA was 20/30 in each eye and IOP was 18 mmHg and 16 mmHg in the right and left eye, respectively. Slit-lamp examination revealed 1+ and trace inflammatory cell in the right and left eye, respectively, with a single synechia also forming in the right eye. He refused a dilated fundoscopic exam at the time, but there was no anterior vitreous cell noted on undilated exam. Prednisolone acetate 1% and cyclopentolate 1% were each started at three times daily. The patient was subsequently lost to follow up with the ophthalmology department due to issues with insurance coverage, but ultimately required increased frequency of ustekinumab dosing to every 4 weeks for systemic control and, when reached by phone, denied recurrence of uveitis symptoms at this dosing despite discontinuation of topical steroids.


  Discussion Top


Ustekinumab is an IL-inhibitor approved for use in four inflammatory conditions, namely psoriasis, PsA, CD, and UC.[1] Since its approval, ustekinumab has proven effective in many who failed or were intolerant to conventional disease-modifying anti-rheumatic drugs or TNF α antagonists, and it is currently under investigation as a treatment for uveitis.[1]

These cases may represent a need for higher dosing of ustekinumab for uveitis than for systemic indications, a pattern which has been seen with other biologic agents. Adalimumab often requires weekly rather than biweekly dosing in treatment of uveitis, and infliximab is generally dosed at 6-10 mg/kg every 4 weeks rather than the 5 mg/kg every 4-8 weeks dosing used for systemic indications.[4],[5]

There may be another explanation for new-onset uveitis in these patients: multiple reports have linked TNF-inhibitors, particularly etanercept, with paradoxical inflammation of the eye of which some manifestations include a novel or worsening uveitic process.[6] Wendling et al. identified a number of patients found with uveitis related to etanercept; significantly higher than other TNF-inhibitors including adalimumab and infliximab.[7],[8] Paradoxical inflammation with extraocular manifestations, including vitiligo, psoriasis and arthritis, has been implicated with use of ustekinumab.[6] The mechanism of paradoxical inflammation is still poorly understood, but thought to be related to cytokine disequilibrium or inadequate response to therapy.[9]

In this report, we present the first two cases of new-onset IBD-associated anterior uveitis in patients using ustekinumab for systemic disease. Interestingly, one patient developed uveitis nearly 1.5 years after induction, while the other developed uveitis within two months; a similar spectrum of presentation can be seen in those that developed paradoxical vitiligo as well.[10]

While further study of this drug may find that it is also associated with paradoxical eye inflammation, it is our suspicion that these cases demonstrate inadequacy of the standard systemic dosing rather than a paradoxical effect occurring with use of ustekinumab. This hypothesis is limited by our small sample size and limited follow-up, but warrants further investigation in large retro- and prospective studies.


  Conclusion Top


This report presents the first published cases of new-onset uveitis in patients on ustekinumab therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lamb YN, Duggan ST. Ustekinumab: A review in moderate to severe Crohn's disease. Drugs 2017;77:1105-14.  Back to cited text no. 1
    
2.
Mugheddu C, Atzori L, Del Piano M, Lappi A, Pau M, Murgia S, et al. Successful ustekinumab treatment of noninfectious uveitis and concomitant severe psoriatic arthritis and plaque psoriasis. Dermatol Ther 2017;30. doi: 10.1111/dth. 12527. Epub 2017 Aug 18.  Back to cited text no. 2
    
3.
Chateau T, Angioi K, Peyrin-Biroulet L. Two cases of successful ustekinumab treatment for non-infectious uveitis associated with Crohn's disease. J Crohns Colitis 2020;14:571.  Back to cited text no. 3
    
4.
Lee J, Koreishi AF, Zumpf KB, Minkus CL, Goldstein DA. Success of weekly adalimumab in refractory ocular inflammatory disease. Ophthalmology 2020;127:1431-3.  Back to cited text no. 4
    
5.
Angeles-Han ST, Lo MS, Henderson LA, Lerman MA, Abramson L, Cooper AM, et al. Childhood arthritis and rheumatology research alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken) 2019;71:482-91.  Back to cited text no. 5
    
6.
Toussirot É, Aubin F. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: An analytical and comprehensive overview. RMD Open 2016;2:e000239.  Back to cited text no. 6
    
7.
Wendling D, Paccou J, Berthelot J-M, Flipo R-M, Guillaume-Czitrom S, Prati C, et al. New onset of uveitis during anti-tumor necrosis factor treatment for rheumatic diseases. Semin Arthritis Rheum 2011;41:503-10.  Back to cited text no. 7
    
8.
Wendling D, Joshi A, Reilly P, Jalundhwala YJ, Mittal M, Bao Y. Comparing the risk of developing uveitis in patients initiating anti-tumor necrosis factor therapy for ankylosing spondylitis: An analysis of a large US claims database. Curr Med Res Opin 2014;30:2515-21.  Back to cited text no. 8
    
9.
Raffeiner B, Ometto F, Bernardi L, Botsios C, Punzi L. Inefficacy or paradoxical effect? Uveitis in ankylosing spondylitis treated with etanercept. Case Rep Med 2014;2014:471319.  Back to cited text no. 9
    
10.
Méry-Bossard L, Bagny K, Chaby G, Khemis A, Maccari F, Marotte H, et al. New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases. J Eur Acad Dermatol Venereol 2017;31:181-6.  Back to cited text no. 10
    




 

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