Visual manifestations in giant cell arteritis: identification of risk factors from the ARTESER Registry.

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

Optimisation of tocilizumab therapy in giant cell arteritis. A multicentre real-life study of 471 patients.

OBJECTIVES: Tocilizumab (TCZ) is the only biologic therapy approved for giant cell arteritis (GCA). There is general agreement on the initial/maintenance dose, duration of TCZ therapy is not well established. In GiACTA trial, after one year on TCZ, most patients had GCA relapse after withdrawal. The aim of this study is to assess the effectiveness and safety of TCZ therapy optimisation in a large unselected series of patients with GCA in a clinical practice scenario. METHODS: We carried out a multicentre study on 471 GCA patients treated with TCZ. Once prolonged remission was achieved (n=231) and based on a decision between patient and physician, TCZ was optimised (n=125). We compared optimised (TCZOPT) and not optimised (TCZNON-OPT) groups. Prolonged remission defined as normalisation of clinical and laboratory data for 6 months. Optimisation was carried out by decreasing TCZ dose and/or increasing dosing interval. RESULTS: We evaluated 231 GCA patients on TCZ in prolonged remission. At TCZ onset, no differences in demographic, clinical, or laboratory data were observed. First TCZ optimisation was performed after a median follow-up of 12[6-17] months. Intravenous TCZ was optimised from 8 to 4mg/kg/4weeks in 44% patients, while subcutaneous TCZ was optimised from 162mg/w to 162mg/every-other-week in 65% cases. At the end of follow-up, prolonged remission (78.2% vs. 84.2%; p=0.29) and relapses (5.6% vs. 10.4%, p=0.177) were similar in TCZOPT vs. TCZNON-OPT. Severe infections were more frequent in TCZNON-OPT (12.9% vs. 6.6%; p=0.009). CONCLUSIONS: TCZ optimisation may be done once complete remission is achieved by reducing dose or increasing dosing interval. This seems to be effective, safe and cost-effective therapeutic scheme.

Abatacept in monotherapy vs combined in interstitial lung disease of rheumatoid arthritis-multicentre study of 263 Caucasian patients.

OBJECTIVE: To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. RESULTS: We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5-15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. CONCLUSION: In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.

Efficacy and safety of switching Jak inhibitors in rheumatoid arthritis: an observational study.

OBJECTIVES: Different Jak inhibitors (jakinibs) have shown efficacy in rheumatoid arthritis (RA), but in a significant proportion of patients, an insufficient response leads to therapy withdrawal. We describe the efficacy and safety of a second jakinib in patients stopping the first due to insufficient response or side effects. METHODS: This is an observational retrospective multicentric study of 31 patients with RA sequentially treated with baricitinib or tofacitinib in any order in clinical practice in ten medical centres in Spain. RESULTS: We identified 31 patients, sequentially treated with both jakinibs. An equal proportion had received tofacitinib or baricitinib first. Most patients (87%) had previously received one or several bDMARD, median 4 (2-5). Median survival for the first jakinib was 5 (3-8) months, and the reasons for withdrawal were inefficacy in 61% and adverse effects in 39%. Most patients (23/31, 74%) maintained the response to the second jakinib after a mean follow-up of 19.5 (12-24) months. In all 8 patients who discontinued the second jakinib, the reason was inefficacy. The treatment suspension rate was similar among patients that had discontinued the first jakinib for inefficacy (26%) or for adverse effects (25%). CONCLUSIONS: Therapy of RA with a second jakinib seems a safe and efficacious option after discontinuation of the first, either for inefficacy or for side effects.

Apremilast in refractory orogenital ulcers and other manifestations of Behçet's disease. A national multicentre study of 51 cases in clinical practice.

OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Digestive involvement in primary Sjögren's syndrome: analysis from the Sjögrenser registry.

OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Prevalence and factors associated with osteoporosis and fragility fractures in patients with primary Sjögren syndrome.

This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679-90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675-35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003-1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

Histopathologic differences between cutaneous vasculitis associated with severe bacterial infection and cutaneous vasculitis secondary to other causes: study of 52 patients.

OBJECTIVES: To determine if cutaneous vasculitis (CV) associated with severe infection has some histopathologic findings that may help us to differentiate patients with this condition from other patients with CV. METHODS: We reviewed the skin biopsy specimens of patients with leukocytoclastic CV associated with a severe bacterial infection. Histopathologic findings of these patients were compared with those observed in leukocytoclastic CV secondary to other causes. Biopsy-proven leukocytoclastic CV were stratified as follows: group a): CV associated with severe underlying bacterial infection; group b): CV without severe bacterial infection but with systemic involvement; group c): CV without systemic involvement. Slides were reviewed by expert pathologists that were blind to the clinical information. The severity of vascular lesions was measured according to a semiquantitative scale (Hodge index). A comparative study between group a) and the other groups was conducted. RESULTS: group a) included 12 patients (2 women/10 men), mean age± SD 56±15 years; group b) 21 patients (10 women/11 men), 52±18 years; and group c) 19 patients (12 women/7 men), 59±24 years. Presence of neutrophilia was significantly increased in biopsies from group a) when compared with the other two groups. Also, a trend to higher frequency of pustular dermatosis was found in patients from group a). Hodge index, degree of inflammatory infiltrate and deep arterioles involvement were similar in all groups. CONCLUSIONS: Neutrophilia is common in skin biopsies of patients with CV associated with severe bacterial infection. No other histopathological findings help us to establish the presence of a severe underlying infection.

Tocilizumab in patients with Takayasu arteritis: a retrospective study and literature review.

OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) in patients with Takayasu arteritis (TA). METHODS: Multicentre open-label retrospective study. RESULTS: Eight patients (all women) with a mean age of 34±16 years, median 36 years (range: 7-57) were assessed. The main clinical features at TCZ therapy onset were: constitutional symptoms (n=4), fever (n=3), headache (n=2), chest pain (n=1), abdominal pain (n=1), mesenteric ischaemia (n=1), myalgia involving the lower limbs (n=1), cerebral vascular insufficiency (n=1), malaise (n=1), upper limb claudication (n=1) and nodular scleritis (n=1). Besides corticosteroids and before TCZ treatment onset, 7 of 8 patients had also received several conventional immunosuppressive and/or biologic agents. Seven patients experienced marked clinical improvement in the first 3 months after the onset of TCZ therapy. After a median follow-up of 15.5 [interquartile range-IQR: 12-24] months, 7 patients were asymptomatic. The median C-reactive protein decreased from 3.09 [IQR: 0.5-12] to 0.15 [IQR: 0.1-0.5] mg/dL (p=0.018), and median erythrocyte sedimentation rate from 40 [IQ range: 28-72] to 3 [IQR: 2-5] mm/1st hour (p=0.012). The median dose of prednisone was also tapered from 42.5 [IQR: 25-50] to 2.5 [IQR: 0-7.5] mg/day (p=0.011). However, TCZ had to be discontinued in 1 patient because she developed a systemic lupus erythematosus, and in another patient due to inefficiency. TCZ dose was reduced in a patient because of mild thrombocytopenia. CONCLUSIONS: TCZ appears to be effective in the management of patients with TA, in particular in patients refractory to corticosteroids and/or conventional immunosuppressive drugs.

The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet's disease: results of a multicentre open-label study.

OBJECTIVES: To assess the efficacy of other biologic therapies, different from infliximab (IFX) and adalimumab (ADA), in patients with Behçet's disease uveitis (BU). METHODS: Multicenter study of 124 patients with BU refractory to at least one standard immunosuppressive agent that required IFX or ADA therapy. Patients who had to be switched to another biologic agent due to inefficacy or intolerance to IFX or ADA or patient's decision were assessed. The main outcome measures were the degree of anterior and posterior chamber inflammation and macular thickness. RESULTS: Seven (5.6%) of 124 cases (4 women/3 men; mean age, 43 (range 28- 67) years; 12 affected eyes) were studied. Five of them had been initially treated with ADA and 2 with IFX. The other biologic agents used were golimumab (n=4), tocilizumab (n=2) and rituximab (n=1). The ocular pattern was panuveitis (n=4) or posterior uveitis (n=3). Uveitis was bilateral in 5 patients (71.4%). At baseline, anterior chamber and vitreous inflammation were present in 6 (50%) and 7 (58.3%) of the eyes. All the patients (12 eyes) had macular thickening (OCT>250µm) and 4 of them (7 eyes), cystoid macular edema (OCT>300 µm). Besides reduction anterior chamber and vitreous inflammation, we observed a reduction of OCT values, from 330.4±58.5 µm at the onset of the biological agent to 273±50 µm at month 12 (p=0.06). Six patients achieved a complete remission of uveitis. CONCLUSIONS: The vast majority of patients with BU refractory to standard immunosuppressive drugs are successfully controlled with ADA and/or IFX. Other biologic agents appear to be also useful.

Single-organ cutaneous small-vessel vasculitis according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a study of 60 patients from a series of 766 cutaneous vasculitis cases.

OBJECTIVE: Cutaneous vasculitis (CV) encompasses a wide group of entities characterized by inflammation of skin blood vessels. The term single-organ vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference (CHCC) to define vasculitis affecting a single organ. To our knowledge there are no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV). Our aim was to characterize this entity from a wide series of patients with CV. METHODS: We analysed cases of SoCSVV from a series of 766 patients with CV from a single university referral centre. According to 2012 CHCC, the following conditions were required to define SoCSVV: (i) skin biopsy showing characteristic leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS: We included 60 patients (26 women and 34 men) with a mean age of 56 years. The main precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous infection [17 patients (34%)]. The main clinical manifestations were palpable purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were the main agents prescribed. After a median follow-up of 4 months, complete recovery was observed in all the patients, although relapses occurred in 8% of patients. CONCLUSION: SoCSVV defined according to the 2012 CHCC may be considered a benign disease usually associated with drugs and/or a previous infection.

Golimumab in uveitis previously treated with other anti-TNF-alpha drugs: a retrospective study of three cases from a single centre and literature review.

OBJECTIVES: The aim of this paper is to assess the clinical response to golimumab (GLM) in patients with non-infectious uveitis from a single centre that had previously been treated with other anti-TNF-α drugs. METHODS: A retrospective chart review was carried out of patients with immune-mediated uveitis refractory to standard synthetic immunosuppressive drugs who were treated with GLM at Hospital Universitario Marqués de Valdecilla, Santander (Spain). Patients were included in this study if they had previously been treated with other anti-TNF-α drugs. A literature review of patients with immune-mediated uveitis undergoing GLM therapy was conducted. RESULTS: Three patients (2 men and 1 woman) were included in this study. Two of them were refractory to other anti-TNF-α drugs. The median age of patients was 26 years (range 20-42). Uveitis was bilateral in two patients. The underlying diseases were uveitis associated with HLA-B27 and psoriasis in one case and sarcoidosis in the other two cases. Improvement of the main ocular parameters following GLM therapy was achieved in all cases. After a median follow-up of 3 (range 1-9) months using GLM therapy, none of the patients had experienced new relapses of uveitis. None of them had side effects during treatment with this drug. A literature review disclosed that our observations were in keeping with other reports that showed good response to GLM in 13 of 16 patients with immune-mediated uveitis refractory to other biologic agents. CONCLUSIONS: Although the follow-up was too short in our series, GLM could be an effective and safe therapy for the management of patients with uveitis previously treated with other anti-TNF-α drugs.

Revisiting clinical differences between hypersensitivity vasculitis and Henoch-Schönlein purpura in adults from a defined population.

OBJECTIVES: Hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura (HSP) are the most common entities included within the category of cutaneous vasculitis (CV). Palpable purpura and histological changes characterised by the presence of leukocytoclastic vasculitis are common in both conditions. Therefore, considerable overlap between them is often seen. It is especially true when the CV occurs in adults. To further establish clinical differences between these two conditions, in the present study we assessed the main clinical differences between HV and HSP in a wide and unselected series of adults with CV from a defined population. METHODS: We reviewed the clinical records of 297 consecutive adults (age >20 years) seen at a single centre between January 1975 and December 2012 that were classified as having HSP or HV according to the criteria proposed by Michel et al. (J Rheumatol 1992; 19: 721-8). RESULTS: Based on the inclusion criteria, 102 adult patients (71 men/31 women) were classified as HSP and 195 (104 men/91 women) as HV. The mean age was similar in both groups (55.8±16.5 years in HSP and 56.8±18.3 years in HV). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HV. Both at the beginning of the disease and when the CV was established clinical manifestations were more frequent in patients with HSP than in those with HV. It was the case for gastrointestinal (57.4% vs. 6.8%; p<0.001), joint (51.5% vs. 36.6%; p=0.01) and renal involvement (86.3% vs. 18.3%; p<0.001). Corticosteroid (56.7% vs. 22%; p<0.001) and cytotoxic drug (19.4% vs. 3.2%; p<0.001) use was also more common in patients with HSP. After a median follow-up of 15.5 (interquartile range- IQR; 3-37) months in HSP and 4 (IQR; 2-12) months in HV, the outcome was better in HV than in HSP. In this regard, complete recovery (72.6% vs. 85.4%; p=0.01) was more commonly observed in HV while residual renal involvement (15.3% vs. 4.2%; p<0.001) was more common in HSP. The disease relapsed in 35.3% of patients with HSP and in 24.4% with HV (p=0.07). CONCLUSIONS: Our results confirm the claim that these two diseases presenting with similar cutaneous involvement are certainly two separate entities with greater systemic involvement and less favourable outcome in HSP.

Reappraisal of the 1990 American College of Rheumatology criteria for the classification of cutaneous vasculitis: an analysis based on 766 patients.

OBJECTIVES: The term cutaneous vasculitis (CV) includes a wide and heterogeneous group of entities. The American College of Rheumatology (ACR) established a set of criteria to classify vasculitis in 1990. Our aim was to further investigate into the applicability of these criteria for the classification of patients with primary CV. METHODS: We analysed a large and unselected series of patients with CV attended to a university referral centre from January 1976 to December 2011. Patients were classified according to the methodology and criteria proposed by the ACR1990 core data set. Patients were also classified according to the same ACR 1990 database as proposed by Michel et al. in 1992 to differentiate Henoch-Schönlein purpura (HSP) from hypersensitivity vasculitis (HV). RESULTS: We assessed 766 patients (346 women and 420 men) with a mean age of 34 years. Patients with cutaneous lesions in the setting of conditions different from primary CV were excluded. According to the 1990 ACR criteria, 405 (63.1%) of the 642 patients with primary CV were classified as having HSP and 230 (35.8%) as HV. However, 119 (18.5%) patients fulfilled the ACR 1990 criteria for both entities. In addition, 7 (1.1%) did not meet the ACR 1990 criteria for any of them and, therefore, they were considered as non-classified vasculitis. When patients with primary CV were tested for the Michel et al. criteria, 392 (61.1%) were classified as having HSP and 250 (38.9%) as HV. Frequent discordance between the ACR 1990 and the Michel et al. criteria was observed. It ranged between 18.4 and 21.7% for HSP and 32.2 to 38% for HV. CONCLUSIONS: According to our data, the ACR 1990 criteria are of limited value for the classification of patients with primary CV.

Tocilizumab in uveitis refractory to other biologic drugs: a study of 3 cases and a literature review.

OBJECTIVES: To evaluate the clinical response to Tocilizumab (TCZ) in three patients with non-infectious uveitis refractory to anti-TNF-α drugs. METHODS: Assessment of TCZ-treated patients with immune-mediated uveitis from two Spanish medical referral centers. Uveitis had been refractory to previous standard synthetic immunosuppressive drugs and at least one TNF-α inhibitor. A literature review of patients with immune-mediated uveitis treated with TCZ therapy was also conducted. RESULTS: 3 women (5 eyes) with uveitis refractory to conventional immunosuppressive therapy and at least one anti-TNF-α drug were treated with TCZ. The mean age of the patients was 48.6±16.1 (range 37-67) years. In two cases uveitis was bilateral and in the other unilateral. The underlying diseases were rheumatoid arthritis in one case and Behçet's disease in the other two cases. After a mean follow-up of 7.3±5.7 (range 1-12) months using TCZ therapy, all patients experienced ocular improvement. Also, in 3 eyes inactive intraocular inflammation was achieved. None of the patients had side effects during the period of treatment with this drug. A literature review disclosed that our observations are in keeping with other reports that showed good response to TCZ in 11 of 12 patients with immune-mediated uveitis refractory to other biologic agents. CONCLUSIONS: TCZ appears to be an effective and safe therapy for the management of patients with uveitis refractory to other biologic drugs.

Tocilizumab in refractory aortitis: study on 16 patients and literature review.

OBJECTIVES: Non-infectious aortitis is often refractory to standard immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of aortitis, we assessed the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. METHODS: Review of 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ. RESULTS: The mean age±SD was 51.4±20.1 years. The underlying conditions were: Takayasu arteritis (TakA) (n=7 cases), giant cell arteritis (GCA) (n=7), relapsing polychondritis (RP) (n=1), and aortitis associated with retroperitoneal fibrosis (n=1). TCZ was the first biologic drug used in all patients with GCA and in the patient with aortitis associated with retroperitoneal fibrosis but in only 2 of 7 TakA patients. In the remaining cases anti-TNF inhibitors were prescribed before TCZ (standard dose was 8 mg/kg/iv/4 weeks). After a mean±SD follow-up of 11.8±6.6 months most patients experienced clinical improvement, showing reduction of erythrocyte sedimentation rate from 43±36 mm/1st h to 5±4 mm/1st h at last visit. At TCZ onset, 25% of patients had fever and 19% polymyalgia rheumatica. These manifestations disappeared after 3 months of TCZ therapy. A corticosteroid sparing effect was also achieved (from 27.3±17.6 mg/day of prednisone at TCZ onset to 4.2±3.8 mg/day at last visit). TCZ had to be discontinued in a patient because of severe neutropenia. CONCLUSIONS: TCZ appears to be effective and relatively safe in patients with inflammatory aortitis refractory to corticosteroids or to other biologic immunosuppressive drugs.