Martina Kron

Adalimumab in Patients with Active Noninfectious Uveitis.

BACKGROUNDnPatients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.nnnMETHODSnThis multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.nnnRESULTSnThe median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).nnnCONCLUSIONSnIn our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial

BACKGROUNDnNon-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids.nnnMETHODSnWe did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838.nnnFINDINGSnBetween Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group).nnnINTERPRETATIONnAdalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis.nnnFUNDINGnAbbVie.

Association of Disorganization of Retinal Inner Layers With Visual Acuity In Eyes With Uveitic Cystoid Macular Edema

PURPOSEnTo determine whether disorganization of retinal inner layers (DRIL) assessed by spectral-domain optical coherence tomography (SDOCT) correlates with visual acuity (VA) in eyes with uveitic cystoid macular edema (CME).nnnDESIGNnSecondary analysis of randomized clinical trial data.nnnMETHODSnFifty-six eyes of 42 patients with uveiticxa0CME were prospectively imaged as part of thexa0VISUAL-1 trial (Clinicaltrials.gov identifier NCT01138657). Central subfield thickness (CFT), horizontal and vertical extent of DRIL, foveal DRIL (>500xa0μm DRIL) hyperreflective foci (HRF), average and largest area of intraretinal (IR) cysts, and extent of disruption of external limiting membrane (ELM) and ellipsoid zone (EZ) were determined within the 1-mm central subfield and correlated with VA at baseline and follow-up visits.nnnRESULTSnRegression analysis adjusted for clustered observations was used to examine the association between OCT morphologic parameters and VA. Across all visits (nxa0= 168), significant associations were found for CFT (0.080 per 100xa0μm, P < .001), foveal DRIL (0.170, P < .001), horizontal DRIL length (0.055 per 100xa0μm, P < .001), vertical DRIL extent (0.001, Pxa0= .005), total area of IR cysts (0.204 per mm2, P < .001), area of largest IR cyst (1.407 per mm2, Pxa0< .001), presence of HRF (Pxa0= .026), and EZ disruption (0.042 per 100xa0μm, Pxa0= .02). ELM disruption did not show a significant association with VA (-0.013 per 100xa0μm, Pxa0= .61).nnnCONCLUSIONnDRIL is a robust and easily obtained surrogate marker of VA in participants with current or resolved uveitic CME. CFT, DRIL, IR cyst area, EZ disruption, and HRF had a strong association with VA.

SAT0523 Adalimumab in Patients with Active, Non-Infectious Uveitis Requiring High-Dose Corticosteroids: the Visual-1 Trial

Background Corticosteroids, currently the mainstay of uveitis treatment, are associated with unwanted side effects, and are not always fully effective. Accordingly, there is a clear unmet need for steroid-sparing treatments. Multiple reports describe the use of biologics, including adalimumab (ADA), in the management of non-infectious uveitis as steroid-sparing agents, but there is a paucity of level 1 evidence to support efficacy of these drugs. Objectives To assess ADA efficacy and safety in patients with active, sight-threatening, non-infectious uveitis despite systemic high-dose corticosteroid therapy. Methods This multinational, double-masked trial included patients aged ≥18 years with active, non-infectious intermediate, posterior, or panuveitis on ≥2 weeks of prednisone (10–60 mg/d). Patients with active uveitis had ≥1 of: active, inflammatory chorioretinal or retinal vascular lesion; anterior chamber (AC) cell grade ≥2+; or vitreous haze (VH) grade ≥2+. Patients were randomized 1:1 to receive placebo or ADA. The ADA group received an 80-mg baseline loading dose and 40 mg every other week for up to 80 weeks; all patients received prednisone 60 mg/d that was tapered to 0 mg by week 15. Primary endpoint was time to treatment failure (TF) in ≥1 eye. TF was defined as ≥1 of: new, active, inflammatory vascular lesions; worsening of BCVA by ≥15 letters at or after week 6; inability to achieve ≤0.5+ AC cell grade or ≤0.5+ VH grade (at week 6); or 2-step increase in AC cell grade or VH grade (after week 6). Ranked secondary endpoints included change in AC cell grade, VH grade, and BCVA from the best state achieved before week 6 to the final visit. Safety was monitored during the trial. Results 217 patients were enrolled (female, 57%; mean age, 42.7 y; mean uveitis duration, 46 mo); 22% had intermediate, 33% had posterior, and 45% had panuveitis. Patients on ADA were less likely to have TF (hazard ratio=0.5; 95% CI, 0.36–0.70; P<0.001) and had fewer causes of TF. Median time to TF was 13 weeks for placebo and 24 weeks for ADA (Figure). Worsening of AC cell grade, VH grade, and BCVA from best state achieved were reduced with ADA compared with placebo (all P<0.05). Adverse event rates were similar in the ADA and placebo groups. Conclusions In patients with active, non-infectious intermediate, posterior, or pan uveitis despite the use of corticosteroids, ADA significantly lowered the risk for uveitic flare or BCVA loss. The safety profile was consistent with the known safety profile across approved ADA indications. Acknowledgements Writing assistance was provided by Jillian Gee and Katherine Groschwitz of Complete Publication Solutions, LLC (CPS), Horsham, PA and Peter Rittenhouse of Complete Healthcare Communications, Inc (CHC), Chadds Ford, PA, on behalf of AbbVie. AbbVie provided funding to CPS and CHC for medical writing assistance. AbbVie funded the study (NCT01138657), contributed to its design and the data analyses, and was involved in the drafting, review, and approval of the abstract. Disclosure of Interest G. Jaffe, MD Consultant for: AbbVie, J. Thorne, MD, PhD Grant/research support from: National Eye Institute and Allergen, Inc., Consultant for: AbbVie, Gilead, and XOMA, D. Scales, MD Consultant for: AbbVie Steering Committee, P. Franco, MD: None declared, S. Tari, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Camez, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Song, MD, MPH Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, M. Kron, PhD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, T. Barisani-Asenbauer, MD, PhD Consultant for: AbbVie Advisory Board, A. Dick, MBBS, MD, FMedSci Consultant for: AbbVie Advisory Board

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III

PURPOSEnTo evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.nnnDESIGNnPhase 3, open-label, multicenter clinical trial extension (VISUAL III).nnnPARTICIPANTSnAdults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF.nnnMETHODSnPatients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 throughxa078.nnnMAIN OUTCOME MEASURESnDisease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff.nnnRESULTSnOf 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials.nnnCONCLUSIONSnPatients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials

ABSTRACT Purpose: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. Methods: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). Results: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40–0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37–0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41–3.54]; VISUAL II: HR = 0.45 [0.20–1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). Conclusions: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

OP0086 Long-term efficacy and safety of adalimumab by immunosuppressant use in patients with non-infectious uveitis in the visual iii trial

Objectives To evaluate the long-term safety and efficacy of adalimumab in patients with non-infectious intermediate, posterior, or panuveitis, by immunosuppressant (IMM) use. Methods Adult patients who completed or had a treatment failure in the VISUAL I/II trials were eligible to enter the Phase III open-label extension study, VISUAL III. Patients received adalimumab 40u2009mg every other week in VISUAL III, and interim follow-up data were collected through Weeks 0 to 78. Efficacy measures assessed included proportion of patients with: no active inflammatory lesions in both eyes; anterior chamber (AC) cell grade ≤0.5 +in both eyes; vitreous haze (VH) grade ≤0.5 +in both eyes; quiescence (defined as no active inflammatory lesions AND AC cell grade ≤0.5 +u2009AND VH grade ≤0.5+); and steroid-free quiescence. Mean steroid dose and mean best corrected visual acuity (BCVA) were also assessed. Missing data were imputed using non-responder imputation for categorical endpoints, last observation carried forward for continuous variables, and as-observed for steroid dose. Efficacy was analysed by IMM (methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine) use. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cut-off date of Oct 31, 2016, with analysis by IMM use. Results Of 371 patients included in the intent-to-treat analysis, 117 (31.5%) were using IMM at VISUAL III baseline (BL) and 30 (8.1%) started IMM during VISUAL III. The proportion of patients with quiescence improved over time irrespective of IMM use; compared with Week 0, 95% confidence intervals were non-overlapping at most time points (figure 1). Numeric improvements were achieved in steroid-free quiescence, steroid dose reduction, and BCVA, with no difference by IMM use. No new safety signals were detected through 130 weeks of treatment and AE rates were generally consistent with previous VISUAL trials; some AEs, notably serious infections and malignancies, were slightly higher with concomitant IMM use.Abstract OP0086 – Figure 1 proportion of patients in quiescence by IMM use in VISUAL?III Conclusions Exploratory analyses from the VISUAL III trial demonstrated that efficacy in adalimumab-treated patients was sustained or improved through 78 weeks of treatment, irrespective of IMM use. AE rates were consistent with previous VISUAL trials, although numerically higher rates for a subset of AEs were observed in patients taking IMM. Acknowledgements AbbVie funded the study and participated in study design, data analysis, and interpretation. AbbVie funded the research and provided writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract; the authors maintained control over the final content. Kevin Hudson, PhD, of 2theNth, provided medical writing support, which was funded by AbbVie Inc. Disclosure of Interest Y. Guex-Crosier Consultant for: AbbVie, Santen, and Novartis, C. S. Foster Grant/research support from: Alcon, Aldeyra, Bausch and Lomb, Clearside Biomedical, Dompe, Icon, Novartis, Santen, Xoma, Aciont, and pSivida, Consultant for: Aldeyra, Bausch and Lomb Surgical, EyeGate, Novartis, pSivida, and Xoma, Speakers bureau: Alcon and Allergan, K. Nakai: None declared, H. Goto Consultant for: AbbVie, K. Douglas Shareholder of: AbbVie, Employee of: AbbVie, S. Pathai Shareholder of: AbbVie, Employee of: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, A. P. Song Shareholder of: AbbVie, Employee of: AbbVie, J. Van Calster Consultant for: Consultant for: advisory boards for AbbVie, Allergan, Santen, and MSD, and has served as a consultant for AbbVie, Allergan, and MSD, A. Adán Consultant for: advisory boards for AbbVie, Santen, Allergan, and Novartis

FRI0618 Adalimumab in non-infectious uveitis – efficacy across different etiologies in the visual i and visual ii trials

Background There is increasing interest in understanding the efficacy of adalimumab across different etiologies of uveitis. No prospective analysis has been conducted to date to determine the efficacy of adalimumab among non-infectious uveitis patients with different etiologies. Objectives To assess adalimumab (ADA) efficacy in active and inactive, non-infectious uveitis across different etiologies in patients who were recruited as part of the VISUAL program. Methods Exploratory data analyses from two global phase 3, double-masked trials: VISUAL I (patients with active uveitis despite ≥2 weeks of prednisone 10–60 mg/day) and VISUAL II (patients with inactive disease dependent on 10–35 mg/day of prednisone to maintain inactivity) were performed. Patients received placebo (PBO) or ADA subcutaneously (80 mg week 0, followed by 40 mg every other week from week 1 up to 80 weeks). In VISUAL I, all patients received a prednisone burst followed by taper to 0 mg by week 15. In VISUAL II, prednisone taper to 0 mg was mandatory by week 19. The primary endpoint was time to treatment failure (TF) at or after week 6 for VISUAL I; and at or after week 2 for VISUAL II1,2. For this analysis, patients were categorized into different uveitis etiologies which they presented at study entry. Hazard ratios (HR) for time to TF were obtained for each uveitis etiology. Results The efficacy of ADA was significantly greater than PBO in the largest subgroup of patients with Idiopathic/other uveitis (VISUAL I: 103 and VISUAL II: 90) etiology in both VISUAL I1 and VISUAL II trials. All other subgroups showed a trend in favor of ADA, except for Sarcoidosis subgroup in the VISUAL II trial (Figure). Overall safety for both trials has been previously reported 1,2. Conclusions These exploratory analyses from the VISUAL I and VISUAL II trials show significantly higher efficacy in ADA-treated patients over PBO in “idiopathic/other” diagnoses of patients with both active and inactive non-infectious uveitis. Furthermore, across different uveitis etiologies, these analyses suggest that ADA-treated patients had a prolonged time to treatment failure compared to PBO. References Jaffe GJ, Dick AD, Brezin AP, et al. N Engl J Med (2016); 375:932–43. Nguyen QD, Merrill PT, Jaffe GJ, et al. The Lancet (2016); 388(10050): 1183–92. Acknowledgements AbbVie funded the VISUAL I and VISUAL II studies and provided writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract. The authors maintained control over the final content. Medical writing assistance was provided by Gaurav Patki, PhD of AbbVie Inc. Disclosure of Interest P. T. Merrill Consultant for: Santen, AbbVie, A. Vitale Consultant for: ACIONT, M. Zierhut Consultant for: AbbVie and Santen, E. Forton Consultant for: AbbVie, Alcon and Allergan, H. Goto Consultant for: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, S. Tari Shareholder of: AbbVie, Employee of: AbbVie, S. Pathai Shareholder of: AbbVie, Employee of: AbbVie

Adalimumab in patients with active and inactive, non-infectious uveitis: VISUAL I and VISUAL II trials

Background Uveitis causes an estimated 10–15% of cases of blindness in western countries and there is an unmet need for effective therapies for patients (pts) with non-infectious uveitis who are at risk for long-term side effects from chronic corticosteroid use. Objectives To assess adalimumab (ADA) efficacy and safety in patients with active and inactive, non-infectious uveitis. Methods Adults with non-infectious intermediate, posterior, or panuveitis were enrolled in two global phase 3, double-masked trials, VISUAL I (pts with active uveitis despite ≥2 weeks (wks) of prednisone (PS), 10–60 mg/d) and VISUAL II (pts with inactive disease dependent on 10–35 mg/d of PS, to maintain inactivity). Pts were randomized 1:1 to receive placebo (PBO) or ADA subcutaneously (80 mg wk 0, followed by 40 mg every other wk from wk 1 up to 80 wks). In VISUAL I, all pts received a PS burst followed by taper to 0 mg by wk 15. In VISUAL II, PS taper to 0 mg was mandatory by wk 19. Integrated data (main study and Japan sub-study) from VISUAL I and VISUAL II trials are reported. The primary endpoint was time to treatment failure (TF) at or after wk 6 for VISUAL I or at or after wk 2 for VISUAL II. Nine ranked secondary endpoints were assessed and adverse events (AEs) were monitored. Results The intent-to-treat (ITT) analyses included 233 (217 main study, 16 Japan sub-study) and 258 (226 main study, 32 Japan sub-study) pts from VISUAL I and VISUAL II, respectively (VISUAL I and VISUAL II: female: 58% and 61%; mean age, 43.2 years (y) and 43.1 y; mean duration of uveitis, 46 months (mt) and 59 mt). Risk of TF was reduced by 44% (VISUAL I) and 48% (VISUAL II) in ADA-treated pts compared to PBO group (VISUAL I: HR=0.56, 95% CI, 0.40–0.76, P<0.001; VISUAL II: HR=0.52, 95% CI, 0.37–0.74, P<0.001). Median time to TF was 3 mt for PBO, 4.8 mt for ADA (VISUAL I) and 5.6 mt for PBO, not estimable for ADA (>18 mt, as more than half of the pts did not achieve TF by wk 80; VISUAL II). ADA-treated pts had fewer TF criteria than PBO in both studies and treatment effects were numerically in favor of ADA for most of the secondary efficacy variables (Table). ADA and PBO AE rates were similar (VISUAL I: 1063 vs 960 events/100 pt-y, VISUAL II: 854 vs 884 events/100 pt-y) in both studies, respectively. Conclusions ADA lowered the risk of uveitic flare or visual acuity loss in pts with active and inactive disease when off PS. The safety profile was consistent with the known safety profile across the approved ADA indications. Acknowledgement AbbVie funded the studies (VISUAL I [NCT01138657] and VISUAL II [NCT01124838]). All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract. The authors maintained control over the final content. Medical writing assistance was provided by Gaurav Patki, PhD of AbbVie Inc. Disclosure of Interest A. P. Brézin Consultant for: AbbVie, A. D. Dick Consultant for: AbbVie, G. J. Jaffe Consultant for: AbbVie, S. Ohno Employee of: AbbVie, Santen, K. Namba Consultant for: AbbVie, H. Goto Consultant for: AbbVie, N. Inomata Shareholder of: AbbVie, Employee of: AbbVie, A. P. Song Shareholder of: AbbVie, Employee of: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, A. Camez Shareholder of: AbbVie, Employee of: AbbVie, S. Tari Shareholder of: AbbVie, Employee of: AbbVie, Q. D. Nguyen Consultant for: AbbVie, Santen, XOMA, Bausch & Lomb