Anti-TNF Agents for Behcet's Disease: Analysis of Published Data on 369 Patients

Objective: Off-label use of anti-tumor necrosis factor (TNF) agents for Behcet’s disease (BD) is increasing. We evaluated published data on their efficacy and safety for patients with unmet medical needs due to severe disease manifestations, including ocular, gastrointestinal, and central nervous system involvement. Methods: Peer-reviewed articles on anti-TNF agents for BD appearing in Medline/PubMed through March 2010 were identified using the appropriate indexing terms. Results: We found 88, 12, and 13 primary articles from 20 countries on infliximab, etanercept, and adalimumab, reporting on 325, 37, and 28 patients, respectively. All patients were inadequately controlled with, or intolerant to, other immunosuppressive regimens, including interferon; 20 patients received more than 1 anti-TNF agent. In the only randomized placebo-controlled trial, 4-week administration of etanercept was effective in suppressing most of the mucocutaneous manifestations. In 16 open prospective studies evaluating the effect of repetitive infliximab injections (174 patients in total, men:women = 3:1, median follow-up = 16.2 months), sustained organ-specific, clinical responses were evident in 90%, 89%, 100%, and 91% of patients with resistant mucocutaneous, ocular, gastrointestinal, and central nervous system involvement, respectively. Combination of infliximab with azathioprine and/or cyclosporine-A appeared superior to monotherapy for sustained ocular remission. However, due to the fact that necessary data were lacking, formal estimation of anti-TNF treatment effect on the disease activity indexes for different organ involvement was not possible. Conclusions: Although more controlled data are needed, there is enough published experience to suggest that TNF blockade represents an important therapeutic advancement for patients with severe and resistant, or intolerant, to standard immunosuppressive regimens BD. (C) 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:61-7

Sleep Disturbances and Interleukin 6 Receptor Inhibition in Rheumatoid Arthritis

Objective. Interleukin 6 (IL-6)-mediated interactions have been associated with sleep disturbances in healthy subjects. In this pilot study we examined whether administration of the IL-6 receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) affects sleep disturbances. Methods. Fifteen patients (13 women) with sleep disturbances at baseline received 6 monthly infusions of tocilizumab 8 mg/kg for moderately or severely active RA. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness by Epworth Sleepiness Scale, disease activity by the 28-joint Disease Activity Score-erythrocyte sedimentation rate, functional disability by Health Assessment Questionnaire Disability Index (HAQ-DI), and fatigue by the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale; FFS) at baseline and first, second, third, and sixth month of treatment. Medications used before enrollment remained unchanged during followup. Results. Sleep quality improved and daytime sleepiness decreased significantly at first-month assessment (p < 0.00001 and p < 0.004, respectively, by repeated measurement analysis) compared to baseline, and these changes became more evident through 6 months. Disease activity decreased, fatigue decreased, and functional status improved significantly. Changes in PSQI score over time were not associated with the corresponding changes in DAS28-ESR (r = 0.37, p = 0.17), but correlated significantly with HAQ-DI changes (r = 0.60, p = 0.02) and marginally with changes in FFS scores (r = -0.46, p = 0.08). Conclusion. Improvement of sleep quality after tocilizumab treatment in patients with RA does not appear to directly result from decreased disease activity, further suggesting that aberrant IL-6 regulation is associated with sleep disturbances. (First Release Dec I 2011; J Rheumatol 2012;39:60-2; doi:10.3899/jrheum.110617

Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade

Inflammatory/metabolic factors and imbalance of haemostasis contribute to cardiovascular disease risk in rheumatoid arthritis (RA). Interleukin-6 (IL-6), a cytokine that plays an important role in immune responses, is implicated in its pathogenesis. In this study, the effects of the IL-6 receptor inhibitor, tocilizumab, on serum adipokines and coagulation/fibrinolysis factors in RA patients were examined. Nineteen consecutive patients (18 women, aged 48 +/- 9 years) received six monthly infusions of 8 mg/kg tocilizumab for moderate or severe RA. Disease activity/severity, as well as serum levels of chemerin apelin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), glucose, insulin and lipids were measured at baseline and at 1, 3 and 6 months thereafter. Chemerin and PAI-1 levels decreased significantly from baseline through 3 to 6 months (from 256 +/- 79 to 174 +/- 12 and 210 +/- 85 ng/ml; from 73 +/- 27 to 56 +/- 22 and 51 +/- 28 pg/ml, respectively). Other adipokines did not change, despite increases in adiposity. In multivariate models, significant independent associations were found between baseline chemerin with age, body mass index, remission of disease, HAQ-Di, CRP and PAI-1. Chemerin decrease at 6 months was significantly associated with PAI-1 and IL-6 changes at 6 months. Baseline PAI-1 associated negatively with remission of disease and total cholesterol, while PAI-1 change at 6 months associated with chemerin changes and smoking status. In conclusion, inhibition of IL-6 signaling in RA favorably alters chemerin and PAI-1 levels in an interrelated manner, despite increasing adiposity. This might represent a dual anti-inflammatory and anti-thrombotic/fibrinolytic mechanism of tocilizumab that may reduce cardiovascular event risk in RA patients

A single infliximab infusion vs corticosteroids for acute panuveitis attacks in Behcet's disease: a comparative 4-week study

Methods. A prospective, observational study of patients with panuveitis, who received either an infliximab infusion (5 mg/kg, 19 eyes) or high-dose methylprednisolone intravenously (1 g/day for 3 days, 8 eyes), or intra-vitreal triamcinolone acetonide (4 mg, 8 eyes) at attack’s onset. Baseline maintenance therapy remained unchanged during the following 30 days. Visual acuity, anterior chamber cells, vitreous cells and inflammation of the posterior eye segment were assessed at baseline and at Days 1, 7, 14 and 29 (+/- 1) post-treatment. Results. While no significant differences were noted between i.v. and intra-vitreal CSs, infliximab was faster than CSs in decreasing total ocular inflammation scores and fundus inflammation scores (P = 0.01 and P < 0.0001 for treatment x time(2) interaction, respectively, using generalized estimating equation analysis). Independently of time, infliximab was superior to CSs in clearing retinal vasculitis (P < 0.003), as well as in resolution of retinitis (P = 0.008) and cystoid macular oedema (P < 0.007). Moreover, a faster regression of cystoid macular oedema was observed with infliximab compared with CSs (P < 0.03). The beneficial effects of the three treatment modalities on visual acuity were comparable from baseline to the end of follow-up. No side effects were noted with infliximab or methylprednisolone, whereas intra-vitreal triamcinolone acetonide caused ocular hypertension in four of the eight eyes, requiring surgical intervention in two. Conclusion. A single infusion of infliximab should always be considered, even as an adjunct therapy, for the control of acute panuveitis attacks in BD

SLICC-Frailty Index is independently associated with impaired physical function, activities of daily living, and quality of life measures.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) was developed to assess health deficits including disease activity, organ damage, comorbidities and functional status. We examined any relationship between SLICC-FI and objective physical function measures, activities of daily living (ADL) performance, and quality of life in Systemic Lupus Erythematosus (SLE). METHODS: SLICC-FI was estimated using data from patient files and patient-reported questionnaires. Jamar Dynamometer, pinch gauge and Purdue pegboard test measured grip strength, pinch strength and dexterity, respectively. ADL performance was assessed by the Disabilities of Arm, Shoulder and Hand (DASH) questionnaire, and Health Assessment Questionnaire (HAQ). Quality of life was evaluated by LupusQol questionnaire. RESULTS: This cross-sectional study included 240 SLE patients (90\% female, mean (SD) age: 47.63 (13.01), median (IQR) disease duration: 9 (4-16). Mean (SD) SLICC-FI was 0.09 (0.06). Forty-three (17.9\%) patients were classified as robust, 105 (43.8\%) as relatively less fit, 77 (32.1\%) as least fit, and 15 (6.2\%) as frail. In univariate analysis, SLICC-FI was significantly associated with DASH and HAQ with an inverse association with grip strength, pinch strength, and all purdue scores (all p {\textless} 0.001). A negative correlation was found between SLICC-FI score and all LupusQoL domain scores (all p {\textless} 0.001). All associations remained statistically significant in multivariate regression analysis, after adjustment for age, disease duration, SLEDAI-2K, SLICC, immunosuppressives, corticosteroids and Charlson score. CONCLUSION: SLICC-FI is independently associated with poor physical function and ADL performance and impaired quality of life and may help to identify patients in need for additional interventions beyond routine care