Ophthalmology Volume 120, Number 12, December 2013 field performance bias” between subjects with lower versus higher CH, but it is difficult to think about an association between hysteresis and perimetric learning, rather than the simple explanation we give.
FELIPE A. MEDEIROS, MD, PhD Department of Ophthalmology, University of California, San Diego, California
Reference 1. Glymour MM, Weuve J, Berkman LF, et al. When is baseline adjustment useful in analyses of change? An example with education and cognitive change. Am J Epidemiol 2005;162:267–78.
Secukinumab in the Treatment of Noninfectious Uveitis Dear Editor: We read with interest the article by Dick et al1 on the efficacy and safety of different doses of secukinumab in patients with noninfectious uveitis in 3 multicenter, randomized, doublemasked, placebo-controlled, dose-ranging, phase III studies in the United States. Although the study suggested secukinumab had a beneficial effect in reducing the use of concomitant immunosuppressive medication, the researchers did not discover any differences in uveitis recurrence between the secukinumab treatment groups and placebo groups. The studies’ authors believed that the relatively small sample size, the differences in the severity of the disease in patients, the differences in the immune expression of interleukin (IL)-17 in individual patients, and the potentially confounding effects of the concomitant immunosuppressive medication may have played roles in the lack of significant differences between the experimental and placebo groups. Not mentioned, however, were 2 points that we believe are pertinent to exploring the efficacy and safety of different doses of secukinumab versus placebo in treating noninfectious uveitis, as well as relevant to the factors that influence the results. In this study, the authors enrolled patients with several types of noninfectious uveitis, including those with Behçet’s disease with posterior uveitis, and patients without Behçet’s disease with active and quiescent noninfectious uveitis. It would have been better if they had taken into account the exact causes of uveitis in the final analysis of how effective the treatment with secukinumab was. As we know, noninfectious uveitis includes Fuchs’ heterochromic iridocyclitis, HLA-B27erelated uveitis, tubulointerstitial nephritis, and uveitis syndrome, as well as systemic disorders associated with uveitis, such as ankylosing spondylitis, Behçet’s disease, juvenile rheumatoid arthritis, and sarcoidosis. Several recent publications reported the application of secukinumab in immune-mediated diseases, but the exact interplay between IL-17 and different kinds of uveitis is unknown. Rich et al2 found that blockade of IL-17 showed a marked alleviation of disease severity in psoriasis. In addition, the reduction of the symptoms of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis
e86
has been observed in secukinumab-treated patients, with no overt warning signs.3 Dysregulation of T helper (Th17) cells may not exist in all autoimmune uveitis. Those who have uveitis with increased numbers of Th17 cells tend to respond to secukinumab treatment. A significant advantage of using secukinumab to treat autoimmune uveitis is that it is effective in patients with noninfectious uveitis refractory to conventional therapy using local or oral corticosteroids.4 In addition, secukinumab also improves visual acuity, ameliorates ocular inflammation, and causes a decrease in the used dose of corticosteroids therapy for these patients. Uveitis is typically treated with glucocorticoid steroids in the form of topical eye drops or oral therapy. In clinical practice, the therapy of noninfectious uveitis has progressed ever since corticoidsparing immunosuppressive agents begun to be used. Although these drugs have decreased corticosteroid-related complications in patients, many cases remain refractory, which has prompted the need for immunosuppressive therapies. The authors also found that secukinumab had the beneficial effect of reducing the use of immunosuppressive medications. We believe further research is warranted to identify the efficiency of secukinumab in managing noninfectious uveitis patients who are refractory to routine immunosuppressive medications.
JIAXU HONG, MD1,2,3 ZUGUO LIU, MD2 XINGHUAI SUN, MD1 JIANJIANG XU, MD1 1 Department of Ophthalmology, and Visual Science, Eye, and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China; 3 Health Communication Institute, Fudan University, Shanghai, China
Financial Disclosures: The authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (2010e2012); National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); National Natural Science Foundation of China (81170817, 81200658); Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai. The sponsor or funding organization had no role in the design or conduct of this research. The authors of the original article declined to respond.
References 1. Dick AD, Tugal-Tutkun I, Foster S, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 2013;120:777–87. 2. Rich P, Sigurgeirsson B, Thaci D, et al. Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study. Br J Dermatol 2013;168:402–11. 3. Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis 2013;72(Suppl 2):116–23. 4. Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010;2:52ra72.
FELIPE A. MEDEIROS, MD, PhD Department of Ophthalmology, University of California, San Diego, California
Reference 1. Glymour MM, Weuve J, Berkman LF, et al. When is baseline adjustment useful in analyses of change? An example with education and cognitive change. Am J Epidemiol 2005;162:267–78.
Secukinumab in the Treatment of Noninfectious Uveitis Dear Editor: We read with interest the article by Dick et al1 on the efficacy and safety of different doses of secukinumab in patients with noninfectious uveitis in 3 multicenter, randomized, doublemasked, placebo-controlled, dose-ranging, phase III studies in the United States. Although the study suggested secukinumab had a beneficial effect in reducing the use of concomitant immunosuppressive medication, the researchers did not discover any differences in uveitis recurrence between the secukinumab treatment groups and placebo groups. The studies’ authors believed that the relatively small sample size, the differences in the severity of the disease in patients, the differences in the immune expression of interleukin (IL)-17 in individual patients, and the potentially confounding effects of the concomitant immunosuppressive medication may have played roles in the lack of significant differences between the experimental and placebo groups. Not mentioned, however, were 2 points that we believe are pertinent to exploring the efficacy and safety of different doses of secukinumab versus placebo in treating noninfectious uveitis, as well as relevant to the factors that influence the results. In this study, the authors enrolled patients with several types of noninfectious uveitis, including those with Behçet’s disease with posterior uveitis, and patients without Behçet’s disease with active and quiescent noninfectious uveitis. It would have been better if they had taken into account the exact causes of uveitis in the final analysis of how effective the treatment with secukinumab was. As we know, noninfectious uveitis includes Fuchs’ heterochromic iridocyclitis, HLA-B27erelated uveitis, tubulointerstitial nephritis, and uveitis syndrome, as well as systemic disorders associated with uveitis, such as ankylosing spondylitis, Behçet’s disease, juvenile rheumatoid arthritis, and sarcoidosis. Several recent publications reported the application of secukinumab in immune-mediated diseases, but the exact interplay between IL-17 and different kinds of uveitis is unknown. Rich et al2 found that blockade of IL-17 showed a marked alleviation of disease severity in psoriasis. In addition, the reduction of the symptoms of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis
e86
has been observed in secukinumab-treated patients, with no overt warning signs.3 Dysregulation of T helper (Th17) cells may not exist in all autoimmune uveitis. Those who have uveitis with increased numbers of Th17 cells tend to respond to secukinumab treatment. A significant advantage of using secukinumab to treat autoimmune uveitis is that it is effective in patients with noninfectious uveitis refractory to conventional therapy using local or oral corticosteroids.4 In addition, secukinumab also improves visual acuity, ameliorates ocular inflammation, and causes a decrease in the used dose of corticosteroids therapy for these patients. Uveitis is typically treated with glucocorticoid steroids in the form of topical eye drops or oral therapy. In clinical practice, the therapy of noninfectious uveitis has progressed ever since corticoidsparing immunosuppressive agents begun to be used. Although these drugs have decreased corticosteroid-related complications in patients, many cases remain refractory, which has prompted the need for immunosuppressive therapies. The authors also found that secukinumab had the beneficial effect of reducing the use of immunosuppressive medications. We believe further research is warranted to identify the efficiency of secukinumab in managing noninfectious uveitis patients who are refractory to routine immunosuppressive medications.
JIAXU HONG, MD1,2,3 ZUGUO LIU, MD2 XINGHUAI SUN, MD1 JIANJIANG XU, MD1 1 Department of Ophthalmology, and Visual Science, Eye, and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China; 3 Health Communication Institute, Fudan University, Shanghai, China
Financial Disclosures: The authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (2010e2012); National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); National Natural Science Foundation of China (81170817, 81200658); Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai. The sponsor or funding organization had no role in the design or conduct of this research. The authors of the original article declined to respond.
References 1. Dick AD, Tugal-Tutkun I, Foster S, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 2013;120:777–87. 2. Rich P, Sigurgeirsson B, Thaci D, et al. Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study. Br J Dermatol 2013;168:402–11. 3. Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis 2013;72(Suppl 2):116–23. 4. Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010;2:52ra72.
