This review summarizes the available evidence regarding the management of refractory non-infectious scleritis with biologic agents. |
Non-infectious scleritis, particularly in its most aggressive forms such as necrotizing scleritis and posterior scleritis, may lead to visual impairment and severe sight-threatening ocular sequelae. |
Monoclonal antibodies targeting tumor necrosis factor alpha, interleukin-6, CD20, and anti-interleukin-1 agents represent reliable options. |
Biologic agents have shown to control scleral inflammation, reduce the overall scleritis relapses, and allow a glucorticoid-sparing effect. |
Management of scleritis must take place in a multidisciplinary setting in order to maximize treatment benefits while minimizing safety concerns. |
Introduction
Research Strategy
Tumor Necrosis Factor Inhibitors
Adalimumab
First author, year reference | Study design | Biologic agent | N° | Type of scleritis | Systemic disease | Results | Safety profile | Mean follow-up (months) |
---|---|---|---|---|---|---|---|---|
Sadhu, 2020 [19] | CS | ADA | 3 | Diffuse AS (n = 1) NAS (n = 2) | RA (n = 1) Idiopathic (n = 2) | Clinical response, GC-sparing effect | NR | 18.5 |
Khalili, 2020 [41] | CR | IFX | 1 | PS + anterior uveitis | Idiopathic | Successful control of inflammation. Improvement in visual acuity. Remission on 4 years. Mild relapse 6 months after IFX cessation responsive to ibuprofen 400 mg 3 times daily | NR | 60 on IFX. 108 in total |
Fabiani, 2020 [11] | RS | ADA (n = 13) IFX (n = 5) GOL (n = 1) | 19 | AS | RA (n = 5), PsA (n = 4), BS (n = 3), idiopathic (n = 3), CD (n = 1), SpA (n = 1), RP (n = 1), Takayasu arteritis (n = 1) | Significant reduction in scleritis grading and ocular relapses Significant GC-sparing effect and stable BCVA Good drug retention rate (almost 60% at 12-month follow-up and an estimated 52% at 36-month follow-up) | Severe urticaria (n = 1), pneumonia and paradoxical psoriasis (n = 1) | 18 |
Amer, 2020 [50] | CR | GOL | 1 | Necrotizing PS | PsA | No disease progression or evidence of association AU or PU or CME | NR | 72 (24 on GOL) |
Iwahashi, 2019 [24] | CS | IFX | 2 | AS (n = 1) AS + PS (n = 1) | RA | Clinical improvement. Treatment discontinuation due to paradoxical ocular AE One patient switched to tocilizumab with complete resolution of scleritis and macular edema | Macular edema and vitreous opacity (n = 1) Exacerbation of PS, dense vitritis and serous retinal detachment (n = 1) | 4.5 |
Dutta Majumder, 2019 [51] | CR | GOL | 1 | NAS | Idiopathic | Proper control of scleritis allowing the insertion of Ahmed glaucoma valve | NR | – |
Durrani, 2017 [17] | RS | ADA | 9 | NS scleritis | NR | Resolution of inflammation in 47% of the eyes with recalcitrant disease and treated with multiple immunosuppressants. GC-sparing effect Cystoid macular edema resolved in 3/4 eyes Discontinuation in 4 patients due to ineffectiveness | Skin reaction (n = 1), rash (n = 1), fatigue and body ache (n = 1), angina (n = 1), swelling of rectus muscles (n = 1), retinal detachment (n = 1) | 31.2 |
Lawuyi, 2016 [16] | CS | ADA | 2 | NAS (n = 2) | RA (n = 1) Idiopathic (n = 1) | Clinical resolution and control of scleral necrosis | Gastroenteritis (n = 1), herpes zoster reactivation (n = 1) | 7.5 |
Sainz-de-la-Maza, 2016 [20] | CS | IFX (n = 5) ADA (n = 5) CZP (n = 1) ETN (n = 1) | 13 | Diffuse AS (n = 10) NAS (n = 3) | RP | IFX and ADA were effective in 1 and 2 patients, respectively. Two patients developed scleritis after IFX therapy and 1 of them was administered ADA and ETN without success. Finally CZP pegol was given, with no further relapses of scleritis | 2 paradoxical scleritis reactions under IFX | 21 |
Akhtar, 2015 [15] | CR | ADA | 1 | AS | Takayasu arteritis | Marked improvement of scleritis, GC-sparing effect | NR | 18 |
Ragam, 2014 [7] | RS | ADA (n = 7)IFX (n = 10) | 17 | Non-necrotizing scleritis | RA (n = 12) RA + CD (n = 2) RA + GD (n = 1) GD (n = 1) CD (n = 1) | Control of active inflammation for at least 2 months was achieved in 88% of patients. Five (29%) patients ended up switching from one TNFα inhibitor to another Stable visual acuity. No significant differences between ADA and IFX | Allergic reaction to a single infusion of IFX (n = 1). Transaminitis on ADA treatment (n = 1) | 25.8 |
Hata, 2012 [40] | CR | IFX | 1 | Nodular scleritis with superficial punctate keratitis | RA | Scleritis and infiltrative keratitis completely improved. No reoccurrence of ocular disease | No side effects | NR |
Sassa, 2012 [48] | CR | ETN | 1 | NS scleritis | RA | Development of scleritis 1 month after ETN reintroduction and reoccurrence during rechallenge. Clinical resolution upon switch to IFX | Paradoxical scleritis after ETN therapy | 100 on ETN, 12 on IFX |
Gaujoux-Viala, 2012 [47] | CS | ETN | 3 | AS with uveitis (n = 2) NAS (n = 1) | RA | Rapid remission after ETN discontinuation. One patient experienced a dechallenge-rechallenge phenomenon | Paradoxical scleritis after ETN therapy | 25.7 |
Tlucek, 2020 [52] | CR | CZP pegol | 1 | NS scleritis | RA | Resolution both symptomatically and on ophthalmological examination | NR | 5 |
Bawazeer, 2011 [14] | CR | ADA | 1 | Nodular AS | Idiopathic | Rapid control of scleritis within 3 months after failure of IFX, GC-sparing effect | No side effects | 60 (24 on ADA) |
Oh, 2011 [39] | CR | IFX | 1 | AS + PS + PUK | Juvenile RA | After the third IFX infusion, the corneal ulceration stopped, and conjunctival hyperemia and ocular discomfort were relieved. Systemic immunosuppression tapered after 3 months | NR | 12 |
Doctor, 2010 [5] | CS/RS | IFX | 10 | Diffuse AS (n = 4) Nodular AS (n = 3) Sclerouveitis (n = 3) CME (n = 1), PUK (n = 1), interstitial keratitis (n = 1), anterior uveitis (n = 1) | Idiopathic (n = 3) RA (n = 2) CD (n = 2) RA + CD (n = 2) BS (n = 1) | Favorable response in 90% of the patients, with 6 of them achieving remission and cessation of concomitant immunosuppression. Monthly infusions may be required to maintain remission | Drug-induced lupus (n = 1) Streptococcal upper respiratory infections (n = 2) Herpes zoster (n = 1) | 16.8 |
Restrepo, 2010 [13] | CR | ADA | 1 | Nodular AS | RA | Control of ocular and extraocular manifestations at 3-month follow-up | 6 | |
Jabbarvand, 2010 [38] | CR | IFX | 1 | NAS + PUK | RP | Complete remission | NR | 12 |
Kontkanen, 2010 [37] | CR | IFX | 1 | NSA | GPA | Rapid clinical response. Improvement in visual acuity | NR | 24 |
Abalos Medina, 2010 [36] | CS | IFX | 1 | NAS | RA | Rapid clinical improvement, resolution of symptoms after the 3rd IFX infusion | NR | 4 |
Herrera-Esparza, 2009 [35] | CR | IFX | 1 | AS | RA | Clinical improvement 2 weeks following the first IFX infusion | No side effects | 24 |
Sen, 2009 [21] | CT | IFX | 5 | AS | HLA-B27 scleritis (n = 1) GPA (n = 1) Cogan’s syndrome (n = 1) Idiopathic (n = 1) | All patients achieved control of active scleritis within 14 weeks. One patient with GPA developed new-onset intraocular inflammation after 14 weeks. Clinical resolution in 4 out of 5 | Ear infection with transient decreased hearing, UTI, lower RTI, and facial rash (n = 1) UTI, diarrhea, upper RTI, nasal congestion and headache, mouth sores, head tremor, occasional numbness and tingling in extremities (n = 1) | 10.8 |
Ahn, 2009 [26] | CS | IFX | 3 | NAS | Idiopathic | Clinical resolution, choroidal and retinal detachment subsided | No complication observed | 16 |
Lopez-Gonzalez, 2009 [34] | CS | IFX | 1 | Necrotizing scleritis | Idiopathic | Clinical response. Inactivity of posterior pole. GC-sparing effect. Preserved visual acuity | No AE | 2.5 |
Le Garrec, 2009 [46] | CS | ETN | 2 | Nodular AS | RA | Development of nodular AS in 2 patients, 17 months and 12 months after ETN initiation, respectively | Paradoxical nodular AS (n = 2) | 14.5 |
Huynh, 2008 [12] | CS | ADA (n = 2), IFX (n = 1) | 3 | NS scleritis | RA (n = 1) Psoriasis (n = 3) | Clinical response, reduction in inflammatory grade | No significant clinical or laboratory AE | 8.5 |
Culver, 2008 [33] | CR | IFX | 1 | PS + orbital miositis | CD | IFX had a partial efficacy on ocular disease and no impact on intestinal symptoms. Two months after cyclophosphamide infusions the patient had a recurrence and was treated with ADA with no further relapses | NR | Roughly 10 |
Morley, 2008 [32] | CS | IFX | 1 | NAS | Surgically induced necrotizing scleritis | IFX discontinuation after the 3rd infusion due to general malaise. Lesion resolved 1 month after IFX cessation | General malaise after 3rd infusion | 2.5 |
Weiss, 2007 [31] | CR | IFX | 1 | PS + papillitis | Idiopathic | Clinical relief in 10 days following the first IFX infusion. Reduction of scleral swelling on B-mode ultrasound examination and regression of papillitis at fundoscopy. Complete remission at 4 months | No side effects | 16 |
Sobrin, 2007 [22] | RS | IFX | 10 | NS scleritis (n = 6) Nodular scleritis (n = 2) Scleritis + anterior uveitis (n = 1) Scleritis + panuveitis (n = 1) | RA (n = 2) CD (n = 1) RP (n = 1) Reactive arthritis (n = 1) Ankylosing spondylitis (n = 1) Idiopathic (n = 4) | Nine out of 10 patient were classified as responders and 1 as partial responder requiring alkylating agent therapy. Five patients were able to reduce their concurrent immunosuppressive therapy. Three patients were able to remain relapse-free while not taking any medication | Lupus-like reaction causing treatment withdrawal (n = 1) | 20 |
Atchia, 2006 [30] | CR | IFX | 1 | NAS + PUK | RA | Dramatic improvement after the first IFX infusion | NR | 5 |
Galor, 2006 [44] | RS | 22 patients with uveitis and scleritis IFX (n = 13) ETN (n = 9) | 4 | AS (n = 3) NAS (n = 1) | RA (n = 2) RP (n = 2) | Two patients developed their first episode of anterior scleritis 8 and 31 months after ETN treatment | Paradoxical AS (n = 1) and NAS (n = 1) after ETN treatment | – |
El-Shabrawi, 2005 [29] | CR | IFX | 1 | NAS + PUK, anterior uveitis | GPA | Clinical improvement, drug-sparing effect, visual acuity improvement | Acute herpes zoster infection | 13 |
Ashok, 2005 [23] | CR | IFX | 1 | NAS + PUK | RA | Dramatic response after three infusions of IFX. Improvement of visual acuity. Relapse upon reduction of prednisolone at 12.5 mg daily. Clinical resolution after increased dosages from 3 mg/kg to 5 mg/kg of IFX | NR | 24 |
Cazabon, 2005 [28] | CR | IFX | 1 | Diffuse AS | RP | Clinical resolution of ocular and systemic manifestations | No AE reported | 6 |
Díaz-Valle, 2004 [27] | CR | IFX | 1 | Diffuse AS | RA | Clinical improvement after the 2nd infusion of IFX. Resolution after 3rd infusion | NR | 6 |
Murphy, 2004 [25] | CS | IFX | 4 | NS scleritis (n = 3) NAS + PUK (n = 1) | RA (n = 1) pANCA renal vasculitis (n = 1) Idiopathic (n = 2) | Three out of 4 patients achieved remission. One patient showed a partial response but treatment was withdrawn. Repeated infusions were required to maintain remission | Infusion-related reaction | 10.5 |
Hernandez-Illas, 2004 [42] | RS | ETN | 10 | Diffuse AS (n = 3) NeS (n = 3) Sectoral diffuse scleritis (n = 1) PUK (n = 1) Recurrent corneoscleral ulcerations (n = 1) Peripheral necrotizing corneal ulcerations (n = 1) | RA (n = 3), GPA (n = 2), PsA (n = 1), CD (n = 1), RP (n = 1), idiopathic (n = 1), arthritis (n = 1) | ETN proved to be effective in resolving scleritis and sterile corneal ulcerations by controlling inflammation, arresting tissue ulceration, and permitting in many cases tapering or cessation of immunosuppressive therapies | No infections or systemic toxicities observed | – |
Tiliakos, 2003 [45] | CS | ETN | 1 | NS scleritis | RA and Sjögren’s syndrome | Development of scleritis 18 months after ETN treatment, treated with local and systemic GC, local cyclosporine and azathioprine. ETN was continued during disease course | Paradoxical scleritis after ETN therapy | 36 |
Smith, 2001 [43] | RS | ETN | 6 | NS scleritis | RA | Scleritis developed in 3 patients under ETN therapy, 1, 2, and 6 months respectively. In the remaining 3 patients, ocular disease was not influenced by TNF blockade (n = 1), remained quiescent (n = 1), or was minimally active (n = 1), | Paradoxical scleritis (n = 3) | – |
Infliximab
Etanercept
Golimumab
Certolizumab Pegol
Anti-CD20 Therapy
Rituximab
First author, year reference | Study design | N° | Type of scleritis | Systemic disease | Results/outcome measures | Safety profile | Mean follow-up (months) |
---|---|---|---|---|---|---|---|
Sadhu, 2020 [19] | Case series | 1 | PS | GPA | Clinical response, GC-sparing effect | NR | 18.5 (3–36) |
Murthy, 2020 [72] | Case series | 1 | NeS with PUK | GPA | Clinical resolution, GC-sparing effect | NR | 18 |
Fabiani, 2020 [79] | Case series | 2 | Diffuse AS (n = 1) PS (n = 1) | Idiopathic (n = 1), GPA (n = 1) | Clinical resolution | No AE | 21 |
Pérez-Jacoiste Asín, 2019 [71] | Case series | 3 | NS scleritis (n = 2) NS scleritis + episcleritis (n = 1) | GPA | Clinical remission | NR | 50.5 |
Ahmed, 2019 [56] | Case series | 8 | AS (n = 2) AS and uveitis (n = 3) AS and PUK (n = 2) AS, PUK, uveitis (n = 1) | GPA | Clinical resolution, improvement or stabilization of visual acuity (expressed in logMAR) in 79% of the eyes. One patient experienced relapse and was re-treated with a second cycle or RTX. Four eyes with NeS required scleral-patch grafting | No side effects | 46.13 |
You, 2018 [58] | Case series | 9 | Diffuse AS (n = 3) Diffuse AS + PS (n = 1) Nodular AS (n = 1) NeS (n = 4) PUK (n = 4), CME (n = 3), uveitis (n = 3) | GPA | All eyes achieved remission with RTX maintenance treatment. Reduction of the modified McCluskey scale. GC-sparing effect. Mild reduction of visual acuity expressed in logMAR. No differences in intraocular pressure between baseline and last follow-up visit | Herpes zoster (n = 1), cytopenia with bronchitis and bacterial pneumonia (n = 1) | 30 (median) |
Fujita, 2018 [70] | Case series | 1 | NS scleritis + PUK + macular edema | GPA | Clinical improvement and stabilization of BCVA | NR | 24 |
Hardy, 2017 [69] | Case series | 1 | NeS + PUK | RA | Clinical resolution, switch to golimumab after 2 years for suboptimal control of articular symptoms | NR | 24 |
Fidelix, 2016 [76] | Case report | 1 | NAS | Surgically induced scleritis | Clinical resolution, VA | NR | 6 |
Kasi, 2016 [68] | Case report | 1 | NeS, serous retinal detachment | IOI and TFIL | Improvement of symptoms and VA | NR | 12 |
Cao, 2016 [8] | Case series | 15 | Sectoral AS (n = 4) Diffuse AS (n = 5) Nodular AS (n = 1) NAS (n = 4), PS (n = 1) | Idiopathic (n = 4) GPA (n = 6) RA (n = 4) UMCTD (n = 1) | Favorable response in 14 patients (93.3%) and significant improvement of McCluskey grading scale for scleritis activity score at 6 months. Steroid-free remission | Infusion hypotension (n = 1) | 34.1 |
Recillas-Gispert, 2015 [57] | Case series | 8 | NAS (n = 5) Nodular AS (n = 1) AS (n = 1) PS + nodular AS (n = 1) | GPA | Clear clinical improvement within 4 weeks after treatment completion, 7 out of 8 achieved remission within 7 months | Community-acquired pneumonia (n = 1) | 30 (median) |
Soon, 2015 [74] | Case report | 1 | PS | CLL | Clinical resolution, improvement of BCVA | NR | 2.5 |
Xu, 2015 [75] | Case report | 1 | NS scleritis, uveitis, optic neuritis | Lymphocytic hypophysitis | Clinical resolution, improvement of VA | NR | 36 |
Joshi, 2015 [55] | Retrospective cohort | 20 | NS scleritis | GPA | Complete and partial remission in 85% and 15% of patients, respectively | Infections (17 events in 6 patients, with 8% requiring hospital admission) Cytopenia (n = 2) Hypogammaglobulinemia requiring intravenous immunoglobulin (n = 2) | 36.5 (median) |
Suhler, 2014 [6] | Clinical trial | 12 | AS (n = 8) AS + orbital disease (n = 2) PS (n = 1) Sclerouveitis (n = 1) | Idiopathic (n = 5) RA (n = 4) GPA and psoriasis (n = 1) Cogan’s syndrome (n = 1) Systemic vasculitis (n = 1) | Reduction in scleritis grading scale, GC-sparing effect, improvement in patient and physician global health score Seven patients experienced relapses after week 24 and received re-treatment with rituximab | Subjective increase of the size of blind spots in one patient and peri-infusional exacerbations of palmar psoriasis in another one | 7 |
Caso, 2014 [73] | Case report | 1 | AS | IgG4-related disease | Clinical resolution | NR | 3 |
Bogdanic-Werner, 2013 [67] | Case series | 2 | NAS (n = 1), PS (n = 1) | Idiopathic | Clinical resolution | No side effects | 17.5 |
Morarji, 2012 [59] | Case report | 1 | NAS | GPA | Clinical resolution (combo therapy with IFX and RTX) | NR | 12 |
Iaccheri, 2010 [66] | Case report | 1 | Nodular AS, AU, acute stromal keratitis | RA | Clinical resolution, relapse and 4th month | NR | 9 |
Bussone, 2010 [61] | Case series | 2 | Nodular AS (n = 1) AS (n = 1) | GPA | Clinical resolution of scleritis | CME (n = 2) | 18 |
Chauhan, 2009 [62] | Case series | 3 | NS scleritis | RA | Clinical resolution | NR | 12 |
Taylor, 2009 [65] | Case series | 6 | NAS (n = 2), AS (n = 1) AS + PS + OG (n = 2) PS + OG (n = 1) | GPA | Clinical remission | No significant side effects and no hospitalizations | 12 (median) |
Kurz, 2009 [64] | Case series | 2 | Nodular AS (n = 1) AS (n = 1) | Idiopathic scleritis (n = 1) RA (n = 1) | Clinical resolution, both patients relapsed once | Itching during infusion | 24 |
Onal, 2008 [63] | Case report | 1 | NeS, AU, and ME | GPA | Clinical resolution, improvement in VA | No AE | 12 |
Ahmadi-Simab, 2005 [54] | Case report | 1 | AS | Sjögren’s syndrome | Resolution of symptoms and symptoms | NR | 6 |
Cheung, 2005 [53] | Case report | 1 | NS scleritis | GPA | Resolution of signs and symptoms on ophthalmological evaluation and GC-sparing effect | NR | 7 |
IL-1 Inhibitors
Anakinra
Gevokizumab
Anti-IL-6 Therapy
Tociluzimab
Other Biologics Agents and Targeted Small Molecules
Abatacept
Ustekinumab
Daclizumab
Alemtuzumab
Tofacitinib
First author, year reference | Study design | Biologic agent/small molecule, N | Type of scleritis | Systemic disease | Results | Safety profile | Mean follow-up (months) |
---|---|---|---|---|---|---|---|
Farhat, 2021 [84] | Case series | TCZ (n = 3) | Diffuse AS (n = 2, 1 with concomitant uveitis) Nodular AS + uveitis (n = 1) | RP | Complete resolution of scleritis | Transient neutropenia (n = 1) | 20 |
Fabiani, 2020 [79] | Case series | ANA (n = 3) ABA (n = 3) TCZ (n = 2) TFC (n = 1) | Nodular AS (n = 1) PS (n = 2) Diffuse AS (n = 6) | Idiopathic (n = 1) RA (n = 6) FMF (n = 1) Psoriatic arthritis (n = 1) | Significant decrease in scleritis grading, in the number of relapses, GC-sparing effect and stable VA | No AE | 16 for ANA 31.7 for ABA 15.5 for TCZ 6 for TFC |
Pyare, 2020 [94] | Case report | TFC (n = 1) | Necrotizing AS | Idiopathic | Resolution of scleral inflammation and remarkable improvement of symptom within 1 month of treatment | Tolerated and no AE | NR |
Poelman, 2020 [83] | Case report | TCZ (n = 1) | AS | GCA | Rapid and sustained remission | No AE | 12 |
Matsumoto, 2020 [89] | Case series | Ustekinumab (n = 1) | NS scleritis | Spondyloarthritis with Crohn’s disease | Clinical improvement | NR | NR |
Iwahashi, 2019 [24] | CS | TCZ (n = 1) | AS + macular edema | RA | Complete resolution after a paradoxical posterior inflammation induced by infliximab | NR | 12 |
Paley 2018 [93] | Case report | TFC (n = 1) | NS scleritis | Idiopathic | Resolution of scleritis within 3 weeks | NR | 9 |
Bottin, 2018 [9] | Pilot study | ANA (n = 10) | AS (n = 7) AS + PS (n = 3) PUK (n = 1) Uveitis, macular edema, and keratitis (n = 1) | Idiopathic (n = 4) RP (n = 3) RA (n = 1) Psoriatic arthritis (n = 1) Behçet syndrome (n = 1) | Clinical remission in 8 patients within 1 month and in one additional patient within 2 months, significant decrease in ocular relapse rate, GC-sparing effect | ISR (n = 4) Dental abscess (n = 1) | 19.4 |
Michael, 2017 [86] | Case report | TCZ (n = 1) | Nodular AS | RA, pyoderma gangrenosum, and SLE | Paradoxical reaction to TCZ. Complete resolution after TCZ withdrawal at 9 months | Nodular AS | – |
Shimizu, 2017 [85] | Case report | TCZ (n = 1) | AS | RP | Sustained remission | NR | 14 |
Knickelbein, 2016 [10] | Clinical trial | Gevokizumab (n = 8) | AS (n = 8) | Idiopathic (n = 6) RA (n = 1) LES and SS (n = 1) | Most eyes (7/9) met the primary outcome with reduction of scleral inflammation grading No changes in intraocular pressure and stable visual acuity | No serious AE, ISR (n = 1), elevated liver enzymes (n = 1), irritable bowel syndrome (n = 3), hypotension (n = 1) | 12 |
Silpa-Archa, 2016 [82] | Case series | TCZ (n = 6) | AS (n = 5) AS + PS (n = 1) | RA (n = 4) Inflammatory bowel disease (n = 1) Idiopathic (n = 1) | Inflammatory control with GC-sparing success in 50% of patients at 9 months and a faster response compared to patients with uveitis | Chest tightness at first 6 h after infusion (n = 1) Serious AE (n = 1) | 14.5 |
Tode, 2015 [81] | Case report | TCZ (n = 1) | Necrotizing AS | Idiopathic | Clinical resolution, stable VA | NR | 24 |
Kommaraju, 2014 [91] | Case report | Alemtuzumab (n = 1) | Diffuse AS | T cell prolymphocytic leukemia | Clinical improvement | Death due to the systemic disease | 19 |
Botsios, 2007 [78] | Case series | ANA (n = 2) | Diffuse AS | RA | Clinical remission and improvement in VA. Dose reduction to alternate days in one patient, caused a scleritis relapse | NR for ANA. Paradoxical diffuse AS under etanercept therapy in 1 patient | 24 |
Papaliodis, 2003 [90] | Case series | Daclizumab (n = 2) | NS scleritis | NS | improvement in inflammation in 1/2 | No serious AE | 11 |