Skip to main content
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 11/2013

01.11.2013 | Inflammatory Disorders

Tocilizumab treatment for refractory uveitis-related cystoid macular edema

verfasst von: Alfredo Adán, Marina Mesquida, Victor Llorenç, Gerard Espinosa, Blanca Molins, Maria V. Hernández, Laura Pelegrín

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 11/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

This retrospective study investigated the efficacy of tocilizumab (TCZ), a fully humanized antibody that binds both to soluble and membrane bound IL-6 receptors, for the treatment of uveitis-related cystoid macular edema (CME) refractory to immunomodulatory therapy.

Methods

Five refractory patients with uveitis-related CME who received TCZ between January and August 2012 were included. All patients received 8 mg/kg TCZ at 4-week intervals. Data regarding patient demographics, use of immunosuppressive drugs, biologic agents or intravitreal therapies prior to TCZ infusions were collected. Main outcome measure was central foveal thickness (CFT) measured by optical coherence tomography at 6 months. Secondary outcome measures were degree of anterior and posterior chamber inflammation (Standardization of Uveitis Nomenclature Working Group criteria) and visual acuity (logarithm of the minimum angle of resolution [log-MAR]) at month 6. Adverse events (AEs) related to TCZ therapy were also assessed.

Results

Eight eyes from five patients (all females) were included. Mean age was 49.4 years (range, 30–68). Mean follow-up was 8.4 months (range, 6–12). Before TCZ, all patients received and failed conventional immunosuppressive therapy and had received at least another biologic agent. Uveitis diagnoses were Birdshot chorioretinopathy (n = 3), juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), and idiopathic panuveitis (n = 1). Mean evolution of CME was 13.4 years (range, 2–30). Mean baseline CFT (95 % confidence interval) was 602 ± 236 μm at baseline, 386 ± 113 μm at month 1 (p = 0.006), 323 ± 103 μm at month 3 (p = 0.026), and 294.5 ± 94.5 μm at month 6 (p = 0.014). Median best-corrected visual acuity (BCVA) improved from 0.66 ± 0.57 at baseline to 0.47 ± 0.62 at month 6 (p = 0.035). After 6 months, an improvement of ≥ 2 lines of BCVA was observed in 50 % of eyes (p = 0.028) remained stable in 25 % and worsened in none of the patients. Sustained uveitis remission was achieved in all patients. No AEs were reported.

Conclusions

These data suggest that TCZ is effective for treating CME in otherwise treatment-refractory cases of uveitis.
Literatur
1.
Zurück zum Zitat Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Opthalmology 113:1146–1149CrossRef Lardenoye CW, van Kooij B, Rothova A (2006) Impact of macular edema on visual acuity in uveitis. Opthalmology 113:1146–1149CrossRef
2.
Zurück zum Zitat Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10:239–246PubMedCrossRef Rothova A (2002) Medical treatment of cystoid macular edema. Ocul Immunol Inflamm 10:239–246PubMedCrossRef
3.
Zurück zum Zitat Díaz Llopis M, Salom D, Garcia de Vicuña C, Cordero Coma M, Ortega G, Ortego N, Suarez de Figueroa M, Rio Pardo MJ, Fernandez-Cid C, Fonollosa A, Blanco R, Garcia-Aparicio AM, Benitez del Castillo JM, Olea JL, Arevalo JF (2012) Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 119:1575–1581PubMedCrossRef Díaz Llopis M, Salom D, Garcia de Vicuña C, Cordero Coma M, Ortega G, Ortego N, Suarez de Figueroa M, Rio Pardo MJ, Fernandez-Cid C, Fonollosa A, Blanco R, Garcia-Aparicio AM, Benitez del Castillo JM, Olea JL, Arevalo JF (2012) Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 119:1575–1581PubMedCrossRef
4.
Zurück zum Zitat Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRef Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRef
5.
Zurück zum Zitat Adán A, Pelegrín L, Rey A, Llorenç V, Mesquida M, Molins B, Ríos J, Keller J (2013) Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients. Retina. 2013 Mar 19. PMID:23514796 Adán A, Pelegrín L, Rey A, Llorenç V, Mesquida M, Molins B, Ríos J, Keller J (2013) Dexamethasone intravitreal implant for treatment of uveitic persistent cystoid macular edema in vitrectomized patients. Retina. 2013 Mar 19. PMID:23514796
6.
Zurück zum Zitat Taylor SR, Lightman SL, Sugar EA, Jaffe GJ, Freeman WR, Altaweel MM, Kozak I, Holbrook JT, Jabs DA, Kempen JH (2012) The impact of macular edema on visual function in intermediate, posterior, and panuveitis. Ocul Immunol Inflamm 20:171–181PubMedCrossRef Taylor SR, Lightman SL, Sugar EA, Jaffe GJ, Freeman WR, Altaweel MM, Kozak I, Holbrook JT, Jabs DA, Kempen JH (2012) The impact of macular edema on visual function in intermediate, posterior, and panuveitis. Ocul Immunol Inflamm 20:171–181PubMedCrossRef
7.
Zurück zum Zitat Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516–1523PubMedCrossRef Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516–1523PubMedCrossRef
8.
Zurück zum Zitat Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140:509–516PubMedCrossRef Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140:509–516PubMedCrossRef
9.
Zurück zum Zitat Nussenblatt RB, Palestine AG, Chan CC, Roberge F (1985) Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 92:467–471PubMed Nussenblatt RB, Palestine AG, Chan CC, Roberge F (1985) Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 92:467–471PubMed
10.
Zurück zum Zitat Tanaka T, Kishimoto T (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci 8:1227–1236PubMedCrossRef Tanaka T, Kishimoto T (2012) Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci 8:1227–1236PubMedCrossRef
11.
Zurück zum Zitat Kramer M, Monselise Y, Bahar I, Cohen Y, Weinberger D, Goldenberg-Cohen N (2007) Serum cytokine levels in active uveitis and remission. Curr Eye Res 32:669–675PubMedCrossRef Kramer M, Monselise Y, Bahar I, Cohen Y, Weinberger D, Goldenberg-Cohen N (2007) Serum cytokine levels in active uveitis and remission. Curr Eye Res 32:669–675PubMedCrossRef
12.
Zurück zum Zitat van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD (2006) Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol 142:192–194PubMedCrossRef van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD (2006) Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol 142:192–194PubMedCrossRef
13.
Zurück zum Zitat Valentincic NV, de Groot-Mijnes JD, Kraut A, Korosec P, Hawlina M, Rothova A (2001) Intraocular and serum cytokine profiles in patients with intermediate uveitis. Mol Vis 17:2003–2010 Valentincic NV, de Groot-Mijnes JD, Kraut A, Korosec P, Hawlina M, Rothova A (2001) Intraocular and serum cytokine profiles in patients with intermediate uveitis. Mol Vis 17:2003–2010
14.
Zurück zum Zitat Kuiper JJ, Mutis T, de Jager W, de Groot-Mijnes JD, Rothova A (2011) Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy. Am J Ophthalmol 152:177–182PubMedCrossRef Kuiper JJ, Mutis T, de Jager W, de Groot-Mijnes JD, Rothova A (2011) Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy. Am J Ophthalmol 152:177–182PubMedCrossRef
15.
Zurück zum Zitat Curnow SJ, Falciani F, Durrani OM, Cheung CM, Ross EJ, Wloka K, Rauz S, Wallace GR, Salmon M, Murray PI (2005) Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 46:4251–4259PubMedCrossRef Curnow SJ, Falciani F, Durrani OM, Cheung CM, Ross EJ, Wloka K, Rauz S, Wallace GR, Salmon M, Murray PI (2005) Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 46:4251–4259PubMedCrossRef
16.
Zurück zum Zitat Ongkosuwito JV, Feron EJ, van Doornik CE, Van der Lelij A, Hoyng CB, La Heij EC, Kijlstra A (1998) Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Invest Ophthalmol Vis Sci 39:2659–2665PubMed Ongkosuwito JV, Feron EJ, van Doornik CE, Van der Lelij A, Hoyng CB, La Heij EC, Kijlstra A (1998) Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Invest Ophthalmol Vis Sci 39:2659–2665PubMed
17.
Zurück zum Zitat Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida A, Yoshimura A (2009) Involvement of Th17 cells and the effect of anti-IL-6. Therapy in autoimmune uveitis. Rheumatology 48:347–354PubMedCrossRef Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida A, Yoshimura A (2009) Involvement of Th17 cells and the effect of anti-IL-6. Therapy in autoimmune uveitis. Rheumatology 48:347–354PubMedCrossRef
18.
Zurück zum Zitat Hohki S, Ohguro N, Haruta H, Nakai K, Terabe F, Serada S, Fujimoto M, Nomura S, Kawahata H, Kishimoto T, Naka T (2010) Blockade of interleukin-6 signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th17 responses. Exp Eye Res 91:162–170PubMedCrossRef Hohki S, Ohguro N, Haruta H, Nakai K, Terabe F, Serada S, Fujimoto M, Nomura S, Kawahata H, Kishimoto T, Naka T (2010) Blockade of interleukin-6 signaling suppresses experimental autoimmune uveoretinitis by the inhibition of inflammatory Th17 responses. Exp Eye Res 91:162–170PubMedCrossRef
19.
Zurück zum Zitat Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot JF, Bron A (2011) Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. Ocul Immunol Inflamm 19:382–383PubMedCrossRef Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot JF, Bron A (2011) Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. Ocul Immunol Inflamm 19:382–383PubMedCrossRef
20.
Zurück zum Zitat Tappeiner C, Heinz C, Ganser G, Heiligenhaus A (2012) Is tocilizumab and effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis? J Rheumatolol 39:1294–1295CrossRef Tappeiner C, Heinz C, Ganser G, Heiligenhaus A (2012) Is tocilizumab and effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis? J Rheumatolol 39:1294–1295CrossRef
21.
Zurück zum Zitat Oshitari T, Kajita F, Tobe A, Itami M, Yotsukura J, Baba T, Yamamoto S (2012) Refractory uveitis in patient with castleman disease successfully treated with tocilizumab. Case Rep Ophthalmol Med. Epub 2012 Nov 6. PMID:23198204 Oshitari T, Kajita F, Tobe A, Itami M, Yotsukura J, Baba T, Yamamoto S (2012) Refractory uveitis in patient with castleman disease successfully treated with tocilizumab. Case Rep Ophthalmol Med. Epub 2012 Nov 6. PMID:23198204
22.
Zurück zum Zitat Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3 Suppl 72):S73–S75PubMed Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3 Suppl 72):S73–S75PubMed
23.
Zurück zum Zitat Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, Ogata A, Yoshizaki K, Kumanogoh A, Kishimoto T, Tanaka T (2012) A case of Behçet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22:298–302PubMedCrossRef Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, Ogata A, Yoshizaki K, Kumanogoh A, Kishimoto T, Tanaka T (2012) A case of Behçet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22:298–302PubMedCrossRef
24.
Zurück zum Zitat Adán A, Llorenç V, Mesquida M, Pelegrín L (2012) Tocilizumab treatment for recalcitrant uveitic macular edema. Graefes Arch Clin Exp Ophthalmol. Dec 28 PMID:23271335 Adán A, Llorenç V, Mesquida M, Pelegrín L (2012) Tocilizumab treatment for recalcitrant uveitic macular edema. Graefes Arch Clin Exp Ophthalmol. Dec 28 PMID:23271335
Metadaten
Titel
Tocilizumab treatment for refractory uveitis-related cystoid macular edema
verfasst von
Alfredo Adán
Marina Mesquida
Victor Llorenç
Gerard Espinosa
Blanca Molins
Maria V. Hernández
Laura Pelegrín
Publikationsdatum
01.11.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 11/2013
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-013-2436-y

Weitere Artikel der Ausgabe 11/2013

Graefe's Archive for Clinical and Experimental Ophthalmology 11/2013 Zur Ausgabe

Letter to the Editor (by invitation)

Hyperopic shift in refraction in adults with aging

Neu im Fachgebiet Augenheilkunde

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.