Conventional Immunomodulatory Therapy Research Articles

Systemic and ocular outcomes in TB-immunoreactive patients receiving immunomodulatory therapy for non-infectious uveitis: a case-control study

BackgroundTuberculosis (TB)-immunoreactivity, measured in vivo (tuberculin skin test (TST)) or in vitro (interferon gamma release assay (IGRA)), can be found in latent, active or even following clearance of TB infection....

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study

Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P<.001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. Observational study. Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.

Outcomes of Intravenous Tocilizumab Treatment for Refractory Pars Planitis

ABSTRACT Purpose To evaluate outcomes of intravenous (IV) tocilizumab (TCZ) in patients with pars planitis refractory to conventional immunomodulatory therapy and anti-tumor necrosis factor (TNF) alpha agents. Methods Medical records of eight patients diagnosed with pars planitis and treated with monthly 4 or 8 mg/kg IV TCZ were reviewed. The primary objective was to initiate and sustain remission continuously for three consecutive months. Secondary outcome measures were changes in best corrected visual acuity (BCVA), degree of anterior chamber (AC) inflammation, vitreous cell, vitreous haze, presence of vitreous or pars plana exudates, peripheral vasculitis, fluorescein angiography (FA) score and central subfieldthickness (CST) on macular optical coherence tomography (OCT). Results Fourteen eyes of eight patients were treated with IV TCZ. Seven patients were women. The average age was 31.35 ± 16.42 years. In 6 (75%) out of 8 patients, IV TCZ, either as monotherapy or in combination with another conventional immunomodulatory agent, induced and sustained remission. The average FA score reduced from 11.15 ± 3.52 at the baseline visit to 6.50 ± 2.12 at the one-year follow-up visit (p-value < 0.05). None of the patients experienced any side effects of IV TCZ. Conclusion IV Tocilizumab (TCZ) may represent an effective and safe treatment option for patients diagnosed with pars planitis resistant to conventional immunomodulatory therapy and anti-TNF alpha agents.

Long-term Experience with Anti-tumor Necrosis factor - α Therapy in the Treatment of Refractory, Non-infectious Intermediate, Posterior, and Panuveitis

ABSTRACT Purpose To study the efficacy and long-term effects of infliximab and adalimumab in patients with active refractory non-infectious intermediate, posterior, or panuveitis (NIPPU). Methods Retrospective, longitudinal study. Results Included were 61 patients (104 eyes) of whom 34 were males (55.74%). Mean age at diagnosis of uveitis was 26.5 ± 16.14 years. All patients had active uveitis at baseline (time of initiation of biological therapy). Median interval between the start of conventional immunomodulatory therapy (IMT) to the introduction of biological therapy was 13.0 (IQR 26.0) months. Ocular inflammation was effectively controlled in 92 eyes (88.46%). The most commonly used TNF-α inhibitor was adalimumab in 47 patients (77%). Mean follow-up time after baseline was 40 ± 34.08 months. In the year preceding the institution of TNF-α inhibitors, the average number of flares was 1.5 ± 1.1/year and it decreased to 0.08 ± 0.29/year in the first year after baseline (p < .0005). Forty-four eyes (42.30%) experienced flare over the entire follow-up period. Mean time to first flare was 14.5 ± 9.26 months. At baseline, the mean dose of prednisone was 25.5-±20.8 mg/day. A marked decrease to a mean prednisone dose of 7.85 ± 9.7 mg/day was observed at 6 months (p = .03). In patients treated with adalimumab, the mean time to prednisone dose ≤7.5 mg/day was 4.02 ± 4.89 months compared to 15.64 ± 21.34 months in patients treated with infliximab (p = .03). 64.3% of patients treated by infliximab had Behçet uveitis compared to 27.7% of patients treated by adalimumab. Eyes treated with adalimumab experienced first flare at a mean time of 14.11 ± 6.29 months, whereas eyes treated with infliximab experienced first flare at 18.29 ± 14.24 months after baseline (p < .0005). The risk for moderate and severe visual loss was lower with shorter duration of uveitis before initiating anti-TNF-α treatment (odds ratio, 0.003; 95% CI, 0.000–0.005; p = .023), better presenting logMAR VA (odds ratio, 0.266; 95% CI, 0.172–0.361; p < .0005) and when adalimumab was used (odds ratio, 0.354; 95% CI, 0.190–0.519, p < .0005). Conclusions Anti-TNF-α therapy was successful in controlling refractory NIPPU in the majority of cases. It significantly reduced flare rate, exerted steroid-sparing effects, and preserved visual potential. Adalimumab use, better initial visual acuity, and earlier introduction of anti-TNF- α therapy were associated with a lower risk of visual loss.

Leukocyte and cytokine variables in asymptomatic Pugs at genetic risk of necrotizing meningoencephalitis.

BackgroundNecrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy.Hypothesis/ObjectivesThat genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs.AnimalsForty Pug dogs asymptomatic for NME from a hospital sample.MethodsProspective observational cohort study, including germline genome‐wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis.ResultsSeven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%‐38%] vs 29% [range, 16%‐41%], P = .03) and higher plasma IL‐10 concentrations than low‐risk Pugs (median 14.11 pg/mL [range, 9.66‐344.19 pg/mL] vs 12.21 pg/mL [range, 2.59‐18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype‐based risk.Conclusions and Clinical ImportanceThese data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.

Immunomodulation and TNF-α inhibition for tubulointerstitial nephritis and uveitis syndrome: a case series

Tubulointerstitial nephritis and uveitis (TINU) syndrome combines acute inflammatory nephritis (AIN) and uveitis. Uveitis in TINU often requires systemic immunomodulatory therapy (IMT), including steroid-sparing agents. Although common for other noninfectious uveitides, the use of tumor necrosis factor-α inhibitors (TNFi) in TINU has seldom been described. This retrospective case series included patients <18years of age with TINU followed at our tertiary care pediatric hospital. Disease characteristics at time of diagnosis and subsequent ophthalmological and rheumatologic evaluations were extracted from the record. AIN was defined as the presence of abnormal renal function and urinalysis or renal biopsy findings consistent with TINU. Uveitis grading, site of inflammation, inactivity, and flare were defined according to Standardization of Uveitis Nomenclature. A total of 10 patients (median age, 12.3years; 6 females) were included. AIN preceded uveitis onset in 6 patients. Uveitis was bilateral at onset in 7 patients. Uveitis inactivity was achieved with systemic corticosteroids (CS) in 2 and with mycophenolate mofetil (MMF) in 3 patients. Because of persistent ocular inflammation, despite CS and IMT, 4 patients were treated with TNFi. All rapidly achieved uveitis quiescence and maintained prolonged inactivity under combined treatment with TNFi and MMF. Most patients in our study cohort required a steroid-sparing immunomodulator to achieve and maintain uveitis control. In the 50% of the cohort in whom conventional IMTs were inadequate, TNFi were able to maintain quiescence. TNF inhibition might be a useful treatment in IMT-refractory uveitis in TINU patients.

Treatment Approaches for Atypical CIDP.

The variants of chronic inflammatory demyelinating polyneuropathy (CIDP) differ not just in their clinical, pathological and electrophysiological characteristics, but often in their indifferent response to conventional immunosuppressive agents which are effective in typical CIDP. High quality evidence is lacking as far as the management of these atypical variants is concerned. In this review, we summarize the treatment approaches to each of these CIDP variants based on existing data. Distal acquired demyelinating symmetric polyneuropathy (DADS) has the phenotype of a symmetric, demyelinating sensory, length-dependent polyneuropathy and is frequently associated with paraproteinemia and anti myelin associated glycoprotein (MAG) antibodies. While the management of idiopathic DADS (DADS-I) is the same as CIDP, DADS-M responds suboptimally and has a favorable response to rituximab. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) manifests as a chronic progressive demyelinating mononeuropathy multiplex which can evolve to a confluent pattern indistinguishable from CIDP. Evidence favors treating MADSAM with conventional immunomodulatory therapy (IMT), but this disorder responds less favorably than CIDP. Some patients present with purely sensory symptoms, known as pure sensory CIDP or chronic inflammatory sensory polyradiculoneuropathy (CISP), the latter localizing to a pre-ganglionic pathology. Both respond well to first line IMT, particularly to intravenous immunoglobulin (IVIG), but patients relapse without maintenance therapy. Pure motor CIDP resembles multifocal motor neuropathy with conduction block (MMNCB), but the previously reported worsening status after steroid treatment was not reproduced in recent studies, and IVIG remains the first-line therapy. Some focal forms of CIDP defy exact classification, but respond well to first-line IMT including IVIG. Overall, atypical CIDP responds to treatment with first-line IMT, but has a suboptimal response compared to CIDP. There is evidence for effectiveness with agents such as rituximab, especially in DADS-M, and this medication can also be used in cases refractory to conventional IMTs. Rituximab is also effective in CIDP with IgG4 antibodies which has distinct clinical features and is mostly refractory to first-line IMT.

Efficacy and Safety of Infliximab in HLA-B27-associated Ocular Inflammation Refractory or Intolerant to Conventional Immunomodulatory Therapy.

PurposeTo determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy.MethodsThis was a retrospective observational case series. All cases were uveitic patients with positive HLA-B27, confirmed through HLA testing, resistant or intolerant to conventional immunomodulatory therapy. The primary outcome of the study was to identify the efficacy of infliximab determined by the control of inflammation, duration of remission, and the ability to reduce conventional immunomodulatory therapy. The secondary outcome was an improvement of two or more lines of best-corrected visual acuity (BCVA) on the Snellen visual acuity chart.ResultsTwenty-four patients (38 eyes) were included in the study. All patients were followed for 24 months. Twenty-one (87.5%) patients completed 24 months of follow-up. Sixteen (66.7%) patients had active uveitis at the beginning of therapy. One patient out of these active patients had active inflammation at the end of follow-up period. Thirteen (87.5%) out of sixteen active patients were in steroid-free remission. The mean duration of treatment to induce remission was 16.5 months (range 6–24 months). Corticosteroid was stopped in 19 (90.5%) patients by the end of the study. At the end of the study, in patients who achieved remission, 14 (58.3%) patients were in remission on infliximab therapy and 6 (25%) patients were in remission off infliximab therapy. Of the 38 eyes, 8 (21.05%) showed improvement in BCVA (three eyes had successful cataract extraction with intraocular lens implantation during infliximab therapy with no subsequent inflammation), while 26 eyes (68.4%) had stable BCVA over the 24-month study period. The side effects included allergic reaction, fatigue, cellulitis, headache, restlessness, elevation of liver enzymes, and anemia. Two patients (n = 24, 8.3%) experienced severe adverse effects and the treatment was stopped prematurely in these two patients.ConclusionInfliximab might induce and maintain the steroid-free remission in HLA-B27-associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy.

P369 Mycobacterium tuberculosis infection among patients with inflammatory bowel disease under biologics: experience of Croatian Tertiary Centre

Abstract Background Mycobacterium tuberculosis infection (TB) causes a huge number of deaths in the world. A majority (95%) of infections remain asymptomatic, defined as latent tuberculosis (LTB). The estimated incidence rate of TB in Croatia is 10.6 cases per 100 000 inhabitants. Patients with inflammatory bowel diseases (IBD) usually require immunosuppressive therapies which puts them at higher risk for infection. LTB diagnosis and prophylactic treatment are recommended for all patients starting biologics. Methods A single-centre retrospective study in the continental part of Croatia included all IBD patients who started treatment with biologics and have presented with TB or LTB from January 2016 till September 2019. The aim was to evaluate the prevalence of LTB among patients with IBD before starting biologic therapy, and TB reactivation during treatment with biologics. All patients underwent Interferon Gamma Release Assay (IGRA) and X-ray. Active infection was excluded or diagnosed using clinical history, bronchoscopy, CT scan and sputum stain for Mycobacteria. Results Study population included 74 patients treated with biologics: 51% female, 73% Crohn’s disease (CD); 37% starting adalimumab, 29% infliximab, 19% ustekinumab and 15% vedolizumab. Prevalence of LTB was 8.1% (6 patients), and all patients underwent isoniazid prophylaxis for 9 months except one patient treated with conventional immunomodulatory therapy which failed prophylactic therapy with both isoniazid and rifampin (liver injury). Among patients with adequate chemoprophylaxis, two patients later on started with anti-TNF therapy (adalimumab), two patients with vedolizumab and one with ustekinumab. One patient with CD and negative LTB screening developed pulmonary TB during induction with infliximab (1 month after initiation); after successful treatment with conventional fourfold therapy, the patient was switched to vedolizumab. During the observational period (median 16 months), all IBD patients with LTB as well with cured TB were in clinical and biochemical remission, without signs of TB (re)activation. Conclusion Our study has demonstrated that prevalence of LTB among our IBD patients starting biologics was significant (8.1%). Treatment with vedolizumab, ustekinumab and anti-TNF (adalimumab) after isoniazid chemoprophylaxis appears to be safe during the observational period, without signs of TB reactivation.

Fuchs’ uveitis masquerading as a Behçet related anterior uveitis

PurposeTo report a case of a Turkish patient with Behçet disease and a recurrent unilateral uveitis.MethodsObservational report of a case of Behçet disease with unilateral anterior uveitis in the left eye (LE). The anterior inflammation was considered as part of the clinical spectrum of Behçet disease. The patient underwent an extensive ophthalmological work‐up.ResultsA 37‐years‐old male Turkish patient presented with an unilateral panuveitis. The Behçet's diagnosis was based on the criteria published by the international study group for Behçet's disease. At presentation the patient reported fatigue, recurrent oral ulcerations and arthralgia. Ophthalmolgical work‐up revealed a visual acuity of 4/10 in the LE. Slit lamp study showed cells in the anterior chamber (AC), vitritis and periflebitis. The panuveitis, refractory to local therapy, was treated with systemic corticosteroids and azathioprine. The posterior inflammation responded well. The anterior segment (AS) showed a chronic, recurrent low‐grade inflammation refractory to conventional immunomodulatory therapy during 8 months. Based upon the therapy‐resistant AS inflammation, the typical diffuse fine stellate keratic participates and the absence of posterior synechiae, the diagnosis of fuchs’ uveitis was suspected. Fundoscopy of the right eye showed hyperpigmented chorioretinal scars, previously related to toxoplasmosis. The clinical picture was highly suggestive for a congenital rubella infection.ConclusionsTo our knowledge this is the first case of a patient with Behçet's disease associated to Fuchs’ uveitis. The refractory anterior inflammation mimicking a Behçet's related AS uveitis is a diagnostic challenge. Ophthalmological work‐up should include an AC punction with Polymerase Chain Reaction to rule out a possible viral genome. As in Hickam's Dictum, one pathology can masque another.

Treatment Results in Serpiginous Choroiditis and Multifocal Serpiginoid Choroiditis Associated with Latent Tuberculosis

Objectives:To compare the results of systemic antitubercular therapy (ATT) and immunomodulatory therapy (IMT) in patients with serpiginous choroiditis (SC) or multifocal serpiginoid choroiditis (MSC).Materials and Methods:The clinical records of 28 patients with SC and MSC were reviewed. Patients were divided into 2 groups according to the treatment applied. Group 1 included 12 patients with MSC and 5 with SC treated with ATT and corticosteroid (CS); group 2 included 9 patients with MSC and 2 with SC treated with conventional IMT, interferon alpha-2a, and/or CS monotherapy.Results:In group 1, clinical remission was achieved in 12/12 MSC and 3/5 SC (total 15/17) patients with administration of ATT for 1 year. Two patients (1 SC, 1 MSC) had reactivation 2 and 7 months after cessation of ATT. Two patients with recurrence after completion of ATT and 2 patients resistant to ATT received IMT ± CS therapy. In group 2, clinical remission was achieved in 7/9 MSC and 2/2 SC (total 9/11) patients after 1 year of treatment. Recurrent inflammation was observed in 2 MSC patients 2 and 112 months after initiation of therapy, but responded well to local/systemic CS or IMT modification, and clinical remission was achieved in 7.8±4.3 months. Cumulative dose of CS was higher in group 2 (p=0.057). Nine of 12 MSC patients treated with ATT and 4/9 MSC patients treated with IMT achieved remission (p=0.203). One of 5 SC patients treated with ATT and 2/2 SC patients treated with IMT achieved remission (p=0.142).Conclusion:Although a statistically significant result could not be achieved in this small case series, our results suggest that ATT may be an appropriate first choice in the treatment of MSC associated with latent tuberculosis, and may be administered in patients with SC who are unresponsive to IMT.

P.192 - Autoimmune myopathy with cardiac involvement associated with antimitochondrial antibodies

Antimitochondrial antibodies (AMA) are associated with primary biliary cirrhosis (PBC). They act against autoantigens situated in the inner membrane of mitochondria. AMA M2, directed against the proteins of the 2–oxo acid dehydrogenase family, is the subtype most frequently associated with hepatic disease. The relation of AMA M2 with inflammatory myopathies has recently been reported by Hashimoto et al, who described 24 patients among 212 patients with seronegative inflammatory myopathy associated with AMA antibodies. We aim to describe a series of patients suffering from immunomediated myopathy (IMM) associated with AMA. We identified 8 patients with IMM. We determined serum CK levels and excluded other specific myositis antibodies. We performed a complete cardiological examination in all patients focused on the presence of arrhythmias. The patients were 7 females and 1 male. Age at onset varied from 31 to 71 years, and diagnosis delay ranged from 1 to 10 years. All patients presented with subacute progressing limb girdle weakness. 6 patients suffered cardiac involvement at onset with supraventricular arrhythmias; 3 of them eventually developed a dilated cardiomyopathy. One patient presented hypercapnic respiratory failure. Three patients presented PBC. Serum CK levels were elevated. Muscle biopsy revealed muscle fiber necrosis in 6 patients. Only in one were perivascular inflammatory infiltrates observed. MHC class I was up-regulated in 6 patients. All patients received immunomodulatory therapy. Muscle weakness improved with steroid treatment but cardiac involvement didn't respond. AMA must be determined in patients suffering with autoimmune myopathy, especially when cardiac manifestations are present. A detailed cardiological examination may be performed in patients with limb girdle weakness associated with AMA. Arrhythmias and dilated cardiomyopathy often fail to respond to conventional immunomodulatory therapy.

Rituximab in the Treatment of Refractory Noninfectious Scleritis

To describe the outcomes of the use of rituximab in the treatment of refractory noninfectious scleritis. Retrospective case series. Review of the medical charts of patients with noninfectious scleritis refractory to conventional immunomodulatory therapy who were seen at the Massachusetts Eye Research and Surgery Institution between 2005 and 2015. The primary outcome measure in this study was steroid-free remission. Secondary outcomes were favorable response (decrease in scleritis activity score) and decrease in steroid dependence. There were 15 patients, with a mean follow-up duration of 34months. Fourteen patients (93.3%) showed a clinical improvement, with 13 (86.6%) achieving a scleritis activity score of zero at 6months. To date, 2 patients continue to enjoy durable drug-free remission (28 and 32months follow-up). There was only 1 adverse effect recorded (infusion hypotension) requiring cessation of rituximab. Rituximab can be an effective treatment modality for recalcitrant noninfectious scleritis and, in some, can result in long-term durable drug-free remission.

LONG-TERM EFFICACY OF SYSTEMIC INFLIXIMAB IN RECALCITRANT RETINAL VASCULITIS.

To evaluate the efficacy of systemic infliximab for the induction of remission in patients with retinal vasculitis, inadequately responsive to other immunomodulatory therapy, based on fluorescein angiography grading for retinal vasculitis evaluation. We analyzed 60 patients with retinal vasculitis, from the Massachusetts Eye Research and Surgery Institution in Cambridge, MA. Response to therapy was based on analysis of serial fluorescein angiography and fundus photography, including a baseline angiogram before initiation of infliximab. Sixty patients received infliximab therapy between July 2007 and July 2012 at Massachusetts Eye Research and Surgery Institution for a diagnosis of retinal vasculitis. All had previously showed a poor clinical response to other immunomodulatory regimens, or ceased therapy due to intolerable side effects. The initial dose of infliximab was 5 mg/kg in all patients and remained at this dose for the extent of treatment in 57 (95%) patients. At 6 months, 45 of 51 (88.23%) patients were maintaining remission with therapy, 5 (9.8%) were in partial remission, and 1 patient had failed. At 12 months, 39 of 39 (100%) patients were maintaining remission with therapy. Infliximab is effective for the treatment of recalcitrant noninfectious retinal vasculitis, refractory to conventional immunomodulatory therapy.

Granulocyte macrophage colony‐stimulating factor treatment of a patient in myasthenic crisis: Effects on regulatory T cells

In this study we describe a patient with a prolonged myasthenic crisis refractory to conventional immunomodulatory therapy who was treated with GM-CSF (granulocyte macrophage colony-stimulating factor, sargramostim). T-regulatory cell (Treg) suppressive function and Foxp3 expression were evaluated before and after treatment with GM-CSF. Treatment with GM-CSF was associated with clinical improvement, expansion in the circulating numbers of Foxp3(+) cells, increase in Foxp3 expression levels in Tregs, early improvement in Treg suppressive capacity for AChR-α-induced T-cell proliferation, and subsequent enhancement in Treg suppression of polyclonal T-cell proliferation. Although definitive conclusions cannot be drawn from a single case, the correlation with similar findings in GM-CSF-treated animals with experimental autoimmune myasthenia gravis suggests further exploration of the effects of GM-CSF in myasthenia gravis should be studied in a clinical trial setting.

Rituximab in the treatment of acquired haemophilia a: a case report

BackgroundAcquired haemophilia A is a very rare disease caused by the development of clotting factor VIII (FVIII) inhibitors, resulting in haemorrhage and bleeding episodes. This situation has been reported during...

Update on peripheral ulcerative keratitis

Ulcerative inflammation of the cornea occurs in the perilimbal cornea, and is associated with autoimmune collagen vascular and arthritic diseases. Rheumatoid arthritis is the most frequent underlying disease. The tendency for peripheral location is due to the distinct morphologic and immunologic characteristics of the limbal conjunctiva, which provides access for circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates immune-mediated vasculitis, and causes inflammatory cell and protein leakage due to vessel wall damage. Development of peripheral ulcerative keratitis associated with systemic disease may represent worsening of a potentially life-threatening disease. Accompanying scleritis, particularly the necrotizing form, is usually observed in severe cases, which may result in corneal perforation and loss of vision. Although first-line treatment with systemic corticosteroids is indicated for acute phases, immunosuppressive and cytotoxic agents are required for treatment of peripheral ulcerative keratitis associated with multisystem disorders. Recently, infliximab, a chimeric antibody against proinflammatory cytokine tumor necrosis factor-alpha, was reported to be effective in cases refractory to conventional immunomodulatory therapy. The potential side effects of these therapies require close follow-up and regular laboratory surveillance.

Systemic Monoclonal Antibody Therapy (Daclizumab) in the Treatment of Cicatrizing Conjunctivitis in Stevens-Johnson Syndrome, Refractory to Conventional Therapy

Purpose: At least one-year follow-up of a case series of young Stevens-Johnson syndrome (SJS) patients with cicatrizing ocular surface disease and recurrent inflammation (SJS-RI) treated with systemic humanized monoclonal antibody (daclizumab).Methods: Five patients (median age 16 yr; range 8–34 yr) with SJS, with recurrent inflammation refractory to conventional immunotherapy, were enrolled in a prospective non-randomized case series study. Inclusion criteria were patients with SJS and ocular cicatrizing inflammatory disease with severe visual impairment, using topical or systemic anti-inflammatory and/or immunomodulatory drugs without clinical improvement resulting in persistent inflammation (SJS-RI). Treatment with Daclizumab 1 mg/Kg (intravenous) was scheduled in three cycles. First cycle with concomitant immunotherapy: a total of 5 doses, with 14 days interval between them (total of this cycle: 10 weeks). Second cycle: interval was increased to 3 weeks; the patients received 2 doses (the second cycle had a total of 6 weeks). Third cycle: maintenance phase with 4 weeks interval between each application, until at least 12 months of the total follow up. After the first cycle (5th dose), the patients were kept with preservative-free lubricants and systemic doxycycline.Results: Control of ocular inflammation was observed at a median of 8 weeks (range 6–10 weeks) in all patients, with relapses in two patients at 20–36 weeks. Relapses were controlled with topical steroids at a median of 10 days, and within 2 weeks the steroids were tapered for both patients.Conclusion: In this small case series, daclizumab demonstrated to play a beneficial role in the control of the inflammatory process of the recurrent inflammation in SJS, refractory to conventional immunomodulatory therapy.

Natalizumab: increased vigilance is required in treating patients with multiple sclerosis

Natalizumab: increased vigilance is required in treating patients with multiple sclerosis

Therapy of Progressive Rheumatoid Arthritis-Associated Corneal Ulceration With Infliximab

To review the relative efficacy of the TNFalpha antagonist infliximab in treating 3 patients with rheumatoid arthritis-associated peripheral ulcerative keratitis. Review of the clinical course of 3 nonconsecutive patients with progressive rheumatoid arthritis-associated peripheral ulcerative keratitis who were initially treated with conventional immunosuppressant therapy and subsequently treated with infliximab. All 3 patients experienced progressive corneal ulceration on oral prednisone and weekly oral or intramuscular methotrexate. They all demonstrated a marked reduction in conjunctival injection, closure of their corneal epithelial defects, and arrest of corneal thinning after receiving infliximab. Two out of 3 patients required patch grafts for treatment of corneal perforations before starting infliximab, and they had no further keratolysis after receiving this agent. Infliximab was effective in arresting progressive rheumatoid arthritis-associated peripheral ulcerative keratitis that was refractory to conventional immunomodulatory therapy.