Ibrutinib-related uveitis: A report of two severe cases

Abstract

Introduction: Ibrutinib is a small-molecule drug approved for the treatment of haematological disorders and is known to be associated with visual disturbances, but uveitis has not yet been reported as an adverse effect of this medication. We present two cases of ibrutinib-associated severe uveitis in patients with chronic lymphocytic leukaemia. Case description: Our first case is a 65-year-old woman who presented with acute onset of bilateral fibrinous anterior uveitis 1 day after starting ibrutinib. Her vision was hand movements in the right eye and 20/120 in the left with hyperaemic discs and subretinal fluid. Ibrutinib was stopped and she experienced a significant improvement under local and oral steroid treatment. The second case is a 64-year-old male with subacute onset of bilateral hypertensive anterior uveitis with pupillary seclusion and right eye hyphaema. He was on ibrutinib for the past 9 months. His vision at presentation was 20/80 and 20/60 for the right and left eye, respectively. He responded poorly to local steroid treatment until ibrutinib was stopped due to cardiac side-effects, after which his uveitis resolved and treatment was stopped. Conclusion: The temporal association between changes in ibrutinib treatment and our patients’ ocular inflammation suggests a causative link. Ibrutinib increases Th1-based immune responses which is proposed as a mechanism for drug-induced uveitis. Its antiplatelet effect may explain the fibrinous nature of the inflammation and hyphaema.

Ocular Complications of Antineoplastic Therapies

“…A case of severe sclerouveitis was described in a case study by Mehraban et al [ 61 ]. This is likewise corroborated by Bohn et al where they reported two severe cases of ibrutinib-related uveitis [ 62 ]. One patient was reported with an acute onset bilateral fibrinous anterior uveitis along with persistent subretinal fluid and hyperemic discs.…”

“…In a study by Bryd et al with a sample size of 391, Ibrutinib was found to have a cataract incidence rate of 3% [ 63 ]. Administration of oral and local topical steroids can be effective in treating symptoms, however, Bohn et al describes a case in which a patient reacted poorly to steroids and cessation of ibrutinib was ordered [ 62 ]. Fu et al , recommends screening with a slit lamp and dilated fundoscopic exam should be conducted [ 64 ].…”

Spontaneous Hyphema during Ibrutinib Treatment in a CLL Patient

“…The reason for ocular disturbances associated with ibrutinib is still unclear, but several mechanisms have been suggested. One case report showed a patient experiencing a spontaneous hyphema, which Bohn and colleagues attributed to ibrutinib's deficiency in platelet adhesion [ 7 ]. Levade et al found in vitro evidence that ibrutinib reduces platelet adhesion to von Willebrand factor and platelet aggregation induced by collagen [ 11 ], supporting this hypothesis.…”

“…Most patients have complete resolution of symptoms upon discontinuation of ibrutinib and topical steroid eye drops (as shown in Table 1 ), similar to our patient. Some case studies have reported changing to different chemotherapeutic agents after discontinuation of ibrutinib [ 7 , 9 ], while others have restarted ibrutinib after their symptoms have resolved [ 2 , 8 ].…”

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

“…To date, ibrutinib-induced uveitis has been reported in only 3 case-reports (Arepalli et al, 2021;Bohn et al, 2021;Mehraban Far et al, 2021), in contrast with the 119 ICSRs documented in VigiBase. Selective pressure for Th1-mediated immunity has been proposed as a mechanism for ibrutinib-associated uveitis (Mehraban Far et al, 2021).…”