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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 913-914

Commentary: Janus kinase inhibitors and juvenile idiopathic arthritis associated uveitis

1 Department of Uveitis and Ocular Immunology Services, Narayana Nethralaya, Bangalore, Karnataka, India
2 Cataract and Refractive Surgery, Narayana Nethralaya, Bangalore, Karnataka, India

Date of Web Publication11-Oct-2022

Correspondence Address:
Dr. Padmamalini Mahendradas
Narayana Nethralaya 121/C, Chord Road, Rajajinagar, 1st 'R' Block, Bangalore - 560 010, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1776_22

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How to cite this article:
Mahendradas P, Mishra SB, Sanjay S, Kawali A, Shetty BK. Commentary: Janus kinase inhibitors and juvenile idiopathic arthritis associated uveitis. Indian J Ophthalmol Case Rep 2022;2:913-4

How to cite this URL:
Mahendradas P, Mishra SB, Sanjay S, Kawali A, Shetty BK. Commentary: Janus kinase inhibitors and juvenile idiopathic arthritis associated uveitis. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Nov 27];2:913-4. Available from: https://www.ijoreports.in/text.asp?2022/2/4/913/358159

We would like to congratulate the authors for reporting the use of tofacitinib as a cost-effective option for refractory juvenile idiopathic arthritis (JIA)-associated uveitis in the developing world.[1]

Cytokines are critical to the pathogenesis of immunological and inflammatory diseases and have thus become the recent therapeutic targets. Targeted, small-molecule therapies such as those that inhibit Janus kinase (JAK) proteins have gained popularity as efficacious options for the treatment of rheumatic and other autoimmune diseases such as rheumatoid arthritis (RA), spondyloarthropathies including juvenile idiopathic arthritis, atopic dermatitis, alopecia areata, psoriasis, and inflammatory bowel disease (IBD).[2]

Juvenile idiopathic arthritis associated uveitis is characterized by persistent destructive intraocular inflammation which can lead to severe visual disability and even blindness.[3] Timely and appropriate treatment is crucial to control permanent ocular damage and complications like band-shaped keratopathy, complicated cataract, macular edema, and hypotony. The authors have reported a case of unilateral chronic recalcitrant anterior uveitis. It is important to acknowledge here that there may be angiographically active peripheral retinal vasculitis without the presence of clinical posterior segment inflammation that can result in complicated cataract formation and hypotony.[4],[5]

Disease-modifying antirheumatic drugs (DMARDs) and particularly the biological DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), including JAK inhibitors can not only prevent progression of joint damage and physical dysfunction but also facilitate remission of the rheumatic diseases.[6] The logical basis underlying the use of these inhibitors is that JAKs play central roles in particular pathological mechanisms making them popular targets for effective disease control. Elucidation of such approaches to regulate JAKs could be an important strategy in addressing the unmet needs in the management of autoimmune diseases.

Boyadzhieva et al.[7] systematically reviewed the published literature regarding the use of JAK inhibitors for autoimmune diseases. They reported frequent adverse effects including upper respiratory tract infections, pneumonia, herpes zoster infection, and viral gastroenteritis. The incidence rates of infections with JAK inhibitors have been reported to be comparable with those for bDMARDs, with the exception of increased rate of herpes zoster infections.[7],[8] Some of the adverse events associated with JAK inhibitors may be predicted by mechanisms involved in the blockade of cytokines that use Janus kinase/signal transducers and activators of transcription (JAK/STAT) for signalling explaining the risk of serious and/or opportunistic infections such as herpes zoster[9] Thus, even though the use of JAK inhibitors can be convenient because of their oral administration and as an affordable alternative as immunosuppressive agents, cautious use of the drugs are warranted with adequate screening to rule out infection, thrombosis, cardiovascular disorders, malignancy, pregnancy, and lactation.[10]

Miserocchi et al.[11] also presented the preliminary results of their study of four consecutive patients with a long history of juvenile idiopathic arthritis and severe associated uveitis treated with JAK inhibitors, namely, baricitinib (three cases) and tofacitinib (one case) where all patients showed improvement of uveitis. Interestingly, they observed a different response to treatment between the uveitis and the articular disease, as the former responded more favorably than the latter. They also reported an overall good safety profile with no occurrence of systemic side effects.[11] We have also used JAK inhibitors in patients with recalcitrant RA associated scleritis and Behcet's disease associated chronic uveitis (unpublished data) and found better outcomes in uveitis associated Behcet's disease and only partial response (persistent congestion with minimal necrosis) in patients with scleritis.

Targeted therapies using mechanism-based approach such as JAK inhibitors can ultimately be used as glucocorticoid-sparing agents to enable complete withdrawal of steroids in some non-infectious or autoimmune uveitis. Nevertheless, in many of these conditions appropriate intensive induction therapies will remain prerequisites for the achievement of disease remission without irreversible damage to the ocular tissues and other vital organs. JAK inhibitors may thus provide a new valuable treatment option in the therapeutic armamentarium for patients with non-infectious uveitis such as JIA-associated uveitis, particularly in refractory cases. The use of JAK inhibitors requires careful consideration of their multitude effects, with adequate antecedent screening and regular post-treatment monitoring for infection, thrombosis, cardiovascular disorders, and malignancy.

  References Top

Babu K, Mooss V, Rao AP. Tofacitinib in juvenile idiopathic arthritis-associated uveitis. Indian J Ophthalmol Case Rep 2022;2:911-2.  Back to cited text no. 1
  [Full text]  
Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 2017;17:78. doi: 10.1038/nrd. 2017.267. Erratum for: Nat Rev Drug Discov 2017;16:843-62.  Back to cited text no. 2
Thorne JE, Woreta F, Kedhar SR, Dunn JP, Jabs DA. Juvenile idiopathic arthritis-associated uveitis: Incidence of ocular complications and visual acuity loss. Am J Ophthalmol 2007;143:840-6.  Back to cited text no. 3
Tripathy K, Ying H, Maldonado Cerda A, Filipowicz A, Kaya M, Seymen Z, et al. Widefield fundus fluorescein angiography features of uveitis associated with juvenile idiopathic arthritis. OculImmunol Inflamm 2022;30:829-38.  Back to cited text no. 4
Mahendradas P, Mishra SB, Mangla R, Sanjay S, Kawali A, Shetty R, et al. Reactivation of juvenile idiopathic arthritis associated uveitis with posterior segment manifestations following anti-SARS-CoV-2 vaccination. J Ophthalmic Inflamm Infect 2022;12:15. doi: 10.1186/s12348-022-00294-2.  Back to cited text no. 5
Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79:685-99.  Back to cited text no. 6
Boyadzhieva Z, Ruffer N, Burmester G, Pankow A, Krusche M. Effectiveness and safety of JAK inhibitors in auto inflammatory diseases: A systematic review. Front Med (Lausanne) 2022;9:930071. doi: 10.3389/fmed. 2022.930071.  Back to cited text no. 7
Conaghan PG, Mysler E, Tanaka Y, Da Silva-Tillmann B, Shaw T, Liu J, et al. Upadacitinib in rheumatoid arthritis: A benefit-risk assessment across a phase III program. Drug Saf 2021;44:515-30.  Back to cited text no. 8
Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol 2017;13:234-43. doi: 10.1038/nrrheum. 2017.23. Erratum in: Nat Rev Rheumatol 2017;13:320.  Back to cited text no. 9
Tanaka Y, Luo Y, O'Shea JJ, Nakayamada S. Janus kinase-targeting therapies in rheumatology: A mechanisms-based approach. Nat Rev Rheumatol 2022;18:133-45.  Back to cited text no. 10
Miserocchi E, Giuffrè C, Cornalba M, Pontikaki I, Cimaz R. JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis. Clin Rheumatol 2020;39:847-51.  Back to cited text no. 11


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