Anti-TNF-a therapy in patients with refractory uveitis due to Behçet's disease: a 1-year follow-up study of 124 patients

Objective: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behçet's disease (BD). Methods: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. Results: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. Conclusion: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.This work was partially supported by the RETICS Program [RD12/0009/0013 (RIER)] from the Instituto de Salud Carlos III (ISCIII), Madrid, Spain.Medicin

Body mass index and disease activity in chronic inflammatory rheumatic diseases: results of the Cardiovascular in Rheumatology (Carma) Project

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients

Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune Mediated Inflammatory Diseases. A Multicenter Study

We aimed to assess the e cacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 13.9 years). The underlying diseases were Bechet?s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean SD BCVA (0.8 0.3 LogMAR vs. 0.6 0.3 LogMAR; p = 0.03), mean SD RNFL (190.5 175.4 m vs. 183.4 139.5 m; p = 0.02), mean SD MT (270.7 23.2 m vs. 369.6 137.4 m; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10?61.5) mg/day at baseline to. 2.5 (0?5) mg/day after one year of follow-up; p = 0.001. After a mean SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is e ective in patients with refractory non-MS ON

Anti-IL-6 Receptor Tocilizumab in Refractory Graves? Orbitopathy: National Multicenter Observational Study of 48 Patients

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the e cacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age standard deviation 51 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 0.25 vs. 0.9 0.16; p = 0.0001), CAS (4.64 1.5 vs. 1.05 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 4.1 vs. 16.73 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 2.1 months, low disease activity (CAS 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or ine cacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Body mass index and disease activity in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology (Carma) project

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients.Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent.Forty-one patients (26women/15 men) were recruited. They had a mean age of 34.414 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n=8), mild leukopenia (n=3), myopathy (n=1), and infections (n=5).ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients.Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent.Forty-one patients (26women/15 men) were recruited. They had a mean age of 34.414 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n=8), mild leukopenia (n=3), myopathy (n=1), and infections (n=5).ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd