Gevokizumab in the Treatment of Autoimmune Non-necrotizing Anterior Scleritis: Results of a Phase I/II Clinical Trial.
OBJECTIVE
To evaluate the safety and potential efficacy of gevokizumab, an anti-interleukin 1β (IL-1β) monoclonal antibody, in the treatment of active, noninfectious, non-necrotizing anterior scleritis.


METHODS
Phase 1/2, open label, nonrandomized, prospective, single-arm pilot trial.


METHODS
Eight patients with active, noninfectious, non-necrotizing anterior scleritis with a scleral inflammatory grade of +1 to +3 in at least 1 eye were enrolled. In 1 patient both eyes were enrolled, for a total of 9 eyes (4 eyes with +1, 1 eye with +2, and 4 eyes with +3). Patients received 1 subcutaneous injection of 60 mg gevokizumab at baseline and then every 4 weeks for 12 weeks. Complete physical and ocular examinations were performed at each visit. The primary outcome was at least a 2-step reduction or reduction to grade 0 in scleral inflammation on a 0 to +4 scale according to a standardized photographic scleritis grading system by 16 weeks in the study eye compared to baseline. Secondary outcomes included changes in visual acuity, intraocular pressure, and trends in scleral grading. Participants who met the primary outcome were eligible to continue in the study for up to 52 weeks and received additional gevokizumab injections every 4 weeks until week 36, followed by 2 safety visits at weeks 40 and 52.


RESULTS
Seven eyes from 7 patients met the primary outcome within a median time of 2 weeks following the first gevokizumab injection. No definitive changes in visual acuity or intraocular pressure were identified. There were no serious adverse events related to the study drug. A total of 43 adverse effects were reported, with 93% described as mild, 95% as nonocular, and only 14% deemed possibly caused by the investigational treatment.


CONCLUSIONS
The results of this small study suggest that blockage of IL-1β using gevokizumab may be beneficial in treating active, noninfectious anterior scleritis and that gevokizumab is well tolerated. Larger randomized trials are warranted to assess the true efficacy of gevokizumab in the treatment of non-necrotizing anterior scleritis.
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Jared E
JE
Knickelbein
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
William R
WR
Tucker
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Nirali
N
Bhatt
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Karen
K
Armbrust
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
David
D
Valent
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Dominic
D
Obiyor
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Robert B
RB
Nussenblatt
National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: senh@nei.nih.gov.
H Nida
HN
Sen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000869:Anterior Eye Segment / Q000000981:diagnostic imaging*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015551:Autoimmunity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015423:Scleritis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014792:Visual Acuity
D061067:Antibodies, Monoclonal, Humanized; C547697:gevokizumab
Ann Rheum Dis. 2012 Apr;71(4):563-6
22084392
Clin Rheumatol. 2016 May;35(5):1281-6
26156661
N Engl J Med. 2012 Dec 20;367 (25):2396-406
23252526
Clin Rheumatol. 2010 May;29(5):559-61
20155432
Ophthalmology. 2003 Sep;110(9):1750-5
13129873
Ophthalmology. 2011 Apr;118(4):768-71
21093921
Ophthalmology. 2005 Aug;112(8):1472-7
16061096
Curr Opin Ophthalmol. 2010 Nov;21(6):463-7
20842032
Scand J Immunol Suppl. 1992;11:171-2
1514036
Am J Ophthalmol. 2009 Oct;148(4):500-509.e2
19570522
Ocul Immunol Inflamm. 2017 Feb;25(1):62-70
26829647
Br J Ophthalmol. 2009 Jul;93(7):984-5
19553514
Ophthalmology. 2010 Mar;117(3):576-84
20031223
Br J Ophthalmol. 2009 Apr;93(4):546-8
19321476
Prog Retin Eye Res. 2013 Jul;35:44-62
23454614
Ophthalmology. 2014 Oct;121(10):1885-91
24953794
Can J Ophthalmol. 2009 Jun;44(3):e9-e12
19506593
Rheumatology (Oxford). 2007 Jun;46(6):1042-3
17449489
Ophthalmology. 2009 Nov;116(11):2188-98.e1
19748676
Nat Rev Rheumatol. 2016 Jan;12(1):14-24
26656658