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

Purpose: To determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy. Methods: This 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. Results: Twenty-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. Conclusion: Infliximab might induce and maintain the steroid-free remission in HLAB27- associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy

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

Purpose: To determine the efficacy and safety of infliximab therapy in patients with HLA B-27-associated ocular inflammation resistant or intolerant to conventional immunomodulatory therapy. Methods: This 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. Results: Twenty-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. Conclusion: Infliximab might induce and maintain the steroid-free remission in HLAB27- associated ocular inflammation in patients resistant or intolerant to conventional immunomodulatory therapy

Interobserver Agreement in Clinical Grading of Vitreous Haze Using Alternative Grading Scales

PURPOSE: To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale vs. the existing 6-step ordinal scale. DESIGN: Evaluation of Diagnostic Test (interobserver agreement study). PARTICIPANTS: 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at one of three large uveitis centers. METHODS: Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. MAIN OUTCOME MEASURES: Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within one or two grades). RESULTS: The scales correlated well (Spearman’s ρ=0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ=0.46 (range 0.28–0.81) and κ=0.40 (range 0.15–0.63), respectively. Within-1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ=0.75 (range 0.66–0.96) and κ=0.62 (range 0.38–0.87), respectively. Within-2-grade agreement for the 9-step scale also was excellent [κ=0.85 (range 0.79–0.92)]. Two-fold more cases were potentially clinical trial eligible based on the 9- than the 6-step scale (p<0.001). CONCLUSIONS: Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (a ≥2 and ≥3 step differences for the 6-step and 9-step scales respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting Reading Center grading may be preferable for clinical trials

Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality

OBJECTIVE: To determine the incidence of all-cause and cancer mortality in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and cancer mortality for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with non-infectious OID, excluding those with HIV infection or pre-existing cancer. INTERVENTIONS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this non-interventional cohort study. MAIN OUTCOMES AND MEASURES: Overall and cancer mortality. RESULTS: Over 187,151 person-years (median follow-up 10.0 years), during which 15,938 patients were at risk for mortality-we observed 1,970 deaths, 435 attributed to cancer. Both patients unexposed to immunosuppressants (Standardized Mortality Ratio (SMR)=0.95, 95% confidence interval (CI): 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SID) (SMR=1.04, 95% CI: 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents versus patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio (aHR)=0.88, 0.89, 0.90, 1.11) and cancer mortality (aHR=1.25, 0.89, 0.89, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3- or 5-year lags, and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and cancer mortality over a median cohort follow-up of 10.0 years. These results suggest safety of these agents with respect to overall and cancer mortality for patients treated with immunosuppression for a wide range of inflammatory diseases