Elsevier

Ophthalmology

Volume 128, Issue 6, June 2021, Pages 899-909
Ophthalmology

Original Article
Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

https://doi.org/10.1016/j.ophtha.2020.10.036Get rights and content
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open access

Purpose

To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.

Design

Open-label, multicenter, phase 3 extension study (VISUAL III).

Participants

Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis).

Methods

Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose.

Main Outcome Measures

Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids.

Results

At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively.

Conclusions

Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Keywords

Adalimumab
Uveitis
Noninfectious uveitis
treatment-emergent adverse event

Abbreviations and Acronyms

AE
adverse event
CNS
central nervous system
logMAR
logarithm of the minimum angle of resolution
MedDRA
Medical Dictionary for Regulatory Activities
MRI
magnetic resonance imaging
PY
patient-years
SAE
serious adverse event
TEAE
treatment-emergent adverse event

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Disclosure(s): All authors have completed and submitted the ICMJE disclosures form. The author(s) have made the following disclosure(s): E.B.S.: Steering committee – AbbVie; Consultant – AbbVie, Clearside, EyeGate, EyePoint, Eyevensys, Gilead, Inotek, Mallinckrodt, Santen, XOMA; Financial support – AbbVie, Aldeyra, Bristol-Myers Squibb, Clearside, EyeGate, EyePoint, Genentech, Novartis. G.J.J.: Consultant – AbbVie, EyePoint Pharmaceuticals, Eyevensys. E.F.: Advisory board and Consultant – AbbVie, Alcon, Allergan; Financial support – AbbVie, Allergan, Gilead. L.L.L.: Advisory board and Consultant – AbbVie, Allergan, Bayer; Financial support – Bayer. P.T.M.: Steering committee – VISUAL studies; Consultant and Advisory board – Alimera, Allergan, EyePoint, Santen; Financial support – AbbVie, Clearside, Gilead, Santen. A.D.D.: Advisory board – AbbVie. A.P.B.: Advisory board and Consultant – AbbVie. Q.D.N.: Scientific advisory board – AbbVie, Bausch & Lomb, Santen, XOMA; Steering committee – VISUAL studies. J.E.T.: Scientific advisory board – AbbVie, Clearside, Santen; Consultant – Gilead, Nightstarx; Financial support – Allergan. J.V.C.: Financial support – Novartis, AbbVie, Allergan, Bayer, DORC, MSD, Novartis, Santen, Zeiss; Nonfinancial support – AbbVie, Allergan, Bayer, DORC, Novartis. L.C.: Consultant – AbbVie, Santen. A.A.: Advisory board – AbbVie, Allergan, Santen. H.G.: Advisory board – AbbVie. T.K.: Advisory board - AbbVie. M.K.: Consultant – AbbVie. A.T.V.: Consultant – AbbVie, Roche. M.K.: Employee – AbbVie Deutschland GmbH & Co. KG. A.P.S.: Employee – AbbVie. J.L.: Employee – AbbVie. S.P.: Former employee – AbbVie. K.M.D.: Employee – AbbVie. A.S.: Advisory board – AbbVie. C.M.: Consultant – AbbVie. M.E.J.V.V.: Lecturer – AbbVie Netherlands, Bayer Netherlands, Novartis Netherlands; Financial support – Allergan Europe. M.Z.: Scientific advisory board – AbbVie, Santen. J.T.R.: Consultant – AbbVie, Celldex, Corvus, Eyevensys, Genentech, Gilead, Horizon, Janssen, Novartis, Regeneron, Roche, Santen, Topivert, UCB; Financial support – Pfizer; Royalties – UpToDate

Sponsored by AbbVie, Inc., North Chicago, Illinois. The sponsor participated in study design and conduct; data management, analysis, and interpretation; and manuscript preparation, review, and approval. Medical writing support was provided by Catherine DeBrosse, PhD, of ICON (North Wales, PA), and was funded by AbbVie Inc.

Data Sharing: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research and will be provided after review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time, and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

HUMAN SUBJECTS: Human subjects were included in this study. Protocol approval was obtained from appropriate review boards before study initiation. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.

No animal subjects were included in this study.

Author Contributions:

Conception and design: N/A

Analysis and interpretation: Suhler, Jaffe, Fortin, Lim, Merrill, Dick, Brezin, Nguyen, Thorne, Van Calster, Cimino, Adan, Goto, Kaburaki, Kramer, Vitale, Kron, Song, Liu, Pathai, Douglas, Schlaen, Muccioli, Van Velthoven, Zierhut, Rosenbaum

Data collection: Suhler, Jaffe, Fortin, Lim, Merrill, Dick, Brezin, Nguyen, Thorne, Van Calster, Cimino, Adan, Goto, Kaburaki, Kramer, Vitale, Schlaen, Muccioli, Van Velthoven, Zierhut, Rosenbaum

Obtained funding: Suhler, Fortin, Lim, Merrill, Thorne, Van Calster, Van Velthoven, Rosenbaum; Study was performed as part of the authors' regular employment duties. No additional funding was provided.

Overall responsibility: Suhler, Jaffe, Fortin, Lim, Merrill, Dick, Brezin, Nguyen, Thorne, Van Calster, Cimino, Adan, Goto, Kaburaki, Kramer, Vitale, Kron, Song, Liu, Pathai, Douglas, Schlaen, Muccioli, Van Velthoven, Zierhut, Rosenbaum