To supplement or not to supplement? The rationale of vitamin D supplementation in systemic lupus erythematosus

© 2018 Nerviani et al. Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal activation of the immune system, chronic inflammation and organ damage. Lupus patients are more prone to be vitamin D deficient. However, current evidence is not conclusive with regards to the role played by vitamin D in SLE development, progression, and clinical manifestations. Objective: Here, we will summarise the current knowledge about vitamin D deficiency prevalence, risk factors, molecular effects, and potential pathogenic role in SLE. We will focus on the link between vitamin D deficiency and lupus clinical manifestations, and on the clinical trials assessing the effects of vitamin D supplementation in SLE. Method: A detailed literature search was performed exploiting the available databases, using “vitamin D and lupus/SLE” as keywords. The relevant interventional trials published over the last decade have been considered and the results are reported here. Conclusion: Several immune cells express vitamin D receptors. Thus, an immunomodulatory role for vitamin D in lupus is plausible. Numerous observational studies have investigated the relationship between vitamin D levels and clinical/serological manifestations of SLE with contrasting results. Negative correlations between vitamin D levels and disease activity, fatigue, renal and cardiovascular disease, and anti-dsDNA titres have been described but not conclusively accepted. In experimental models of lupus, vitamin D supplementation can improve the disease. Interventional trials have assessed the potential therapeutic value of vitamin D in SLE, but further larger studies are needed

Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma.

Omalizumab is a humanized monoclonal anti-IgE antibody approved in 2005 by the European Medicine Agency (EMA) for the treatment of severe persistent allergic asthma, which remains inadequately controlled despite optimal therapy with high doses of inhaled corticosteroids and long-acting β2-adrenergic agonists. Within this context, the present observational study refers to 16 patients currently treated with omalizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti- IgE therapy was started in the period included between March 2007 and February 2010, thus lasting at least 10 months. After 40 weeks of add-on treatment with omalizumab, very relevant decreases were detected, in comparison with pre-treatment mean (± standard deviation) values, in monthly exacerbation numbers (from 1.1 ± 0.6 to 0.2 ± 0.4; p < 0.01) and oral corticosteroid consumption (from 22.6 ± 5.0 to 1.2 ± 2.9 mg/day of prednisone; p < 0.01). These changes were associated with stable improvements in lung function, expressed as increases of both FEV1 (from 53.6 ± 14.6% to 77.0 ± 14.9% of predicted values; p < 0.01) and FEV1/FVC ratio (from 56.3 ± 9.5% to 65.8 ± 9.2%; p < 0.01). Moreover, in 5 patients who persistently had increased numbers of eosinophils (mean ± SD: 15.9 ± 8.0% of total WBC count; absolute number: 1,588.0 ± 956.9/μl) despite a long-lasting therapy with inhaled and systemic corticosteroids, the peripheral counts of these cells decreased down to near normal levels (mean ± SD: 6.3 ± 2.3% of total WBC count; absolute number: 462.0 ± 262.3/μl) after 16 weeks of treatment with omalizumab. Therefore, this descriptive evaluation confirms the efficacy of add-on omalizumab therapy in selected patients with exacerbation-prone, chronic allergic uncontrolled asthma, requiring a continuous intake of oral corticosteroids

Use of ultrasonography to discriminate psoriatic arthritis from fibromyalgia: A post‐hoc analysis of the ulisse study

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray‐scale (GS; B‐mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS‐ and PD‐mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B‐ and PD‐mode, respectively, 3.5 being the best cut‐off GS‐score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B‐mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B‐mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS

POS1061 THE ITALIAN PROSPECTIVE SIRENA STUDY: FOCUS ON EARLY PSORIATIC ARTHRITIS COHORT AND GENDER DIFFERENCES

Background:Limited data on early Psoriatic Arthritis (PsA) are available1,2.Objectives:To describe baseline data of PsA patients naive to any DMARDs.Methods:SIRENA study is an Italian, prospective Registry of Spondyloarthritis patients diagnosed according to ASAS criteria and naïve to any DMARDs. Data on demographic and clinical characteristics of PsA cohort were collected and analysed, also by gender.Results:203/350 (58%) subjects included in SIRENA Registry had PsA (mean age 51.9 years) and in 190/203 (94%) CASPAR classification criteria were fulfilled. In 70% of patients the diagnosis was performed within 24 months from symptom onset. At baseline, 194/203 (95.6%) had mainly peripheral manifestations, 74.4% of patients had skin psoriasis, 40% nail psoriasis, 39.3% clinical enthesitis and 25.9% dactylitis. Mean SJC66 and TJC68 were, respectively, 3 and 7.2; mean PhGA was 46.3; 14.7% of patients were in MDA.The higher tender joint count in women (mean TJC68 9.3 in women vs 5.3 in men) resulted in a higher disease activity according to DAPSA (high disease activity: 11.5% women vs 4.1% men), a higher joint VAS score (mean score 47.1 women vs 39.8 men) and a lower prevalence of MDA (8.3% women vs 20% men). We observed a higher prevalence of moderate or severe psoriasis in men (BSA≥3%: 37% men vs 27.8% women) while all PROs collected (PtGA, pain VAS score, sleep VAS score, BASFI, BASDAI, HAQ-DI, WPAI) were worse in women.The most common comorbidities were cardiometabolic (35.5%), endocrine (9.4%), and gastrointestinal disorders (7.4%). Cardiometabolic disorders were more frequently reported by men, endocrine and gastrointestinal disorders by women; depression exclusively by women.Conclusion:This analysis provides real-life data in a cohort of early PsA subjects. Relevant gender differences were observed, with women showing a higher disease activity and more joint pain and men having more severe psoriasis. Women also perceived a worse disease burden.References:[1]Theander E, et al. Ann Rheum Dis 2014; 73:407–413.[2]Nas K, et al. Mod Rheumatol 2017; 27(2):345-349.Table 1.Baseline dataPsAAll patients (n=203)Women (n=98)Men (n=105)Age (years), mean (SD)51.9 (13.1)51.1 (13.2)52.7 (13.0)Men, n (%)105 (51.7)0 (0)105 (100)BMI (kg/m2), mean (SD)25.9 (4.4)25.4 (4.9)26.4 (3.9)BMI categories^, n (%) Obese40 (21.2)20 (22.2)20 (20.2) Overweight44 (23.3)15 (16.7)29 (29.3) Under/normal weight105 (55.6)55 (61.1)50 (50.5)Comorbidities > 5%*, n (%) Cardiometabolic72 (35.5)28 (28.6)44 (41.9) Endocrine disease19 (9.4)15 (15.3)4 (3.8) Gastrointestinal15 (7.4)10 (10.2)5 (4.8) Depression/Anxiety8 (3.9)8 (8.2)0 (0) Hepatic diseases7 (3.5)1 (1.0)6 (5.7)Clinical assessmentCRP (mg/dl), median (min-max)0.40 (0 – 7.12)0.31 (0 - 5.40)0.49 (0 - 7.12)SJC66, mean (SD)3.0 (4.0)3.2 (4.0)2.7 (4.0)TJC68, mean (SD)7.2 (8.8)9.3 (10.3)5.3 (6.6)Dactylitis, n/tot assessed (%)35/135 (25.9)12/63 (19.1)23/72 (31.9)Enthesitis, n/tot assessed (%)66/168 (39.3)39/80 (48.8)27/88 (30.7)Psoriasis skin, n (%)151 (74.4)68 (69.4)83 (79.1)Psoriasis nails, n/tot assessed (%)62/155 (40.0)29/75 (38.7)33/80 (41.3)Fibromyalgia, n (%)6 (3.0)5 (5.2)1 (1.0)VAS, mean (SD) [range: 0-100] PhGA score46.3 (25.8)51.2 (25.4)41.7 (25.4) Joint score43.3 (26.8)47.1 (25.2)39.8 (27.8) Skin score20.3 (24.0)17.8 (23.1)22.6 (24.8)DAPSA, mean (SD)22.3 (14.1)26.8 (15.4)18.7 (11.9)DAPSA categories^, n (%)High disease activity13 (7.4)9 (11.5)4 (4.1)Moderate disease activity83 (47.2)43 (55.1)40 (40.8)Low disease activity71 (40.3)24 (30.8)47 (48.0)Remission9 (5.1)2 (2.6)7 (7.1)MDA°, n (%)23 (14.7)6 (8.3)17 (20.0)BSA categories, n (%) 3-10% (moderate psoriasis)35 (24.6)13 (21.2)22 (27.1) >10% (severe psoriasis)12 (8.5)4 (6.6)8 (9.9)* A patient could report one or more comorbidities. ^The sum does not add up to the total because of some missing values. ° According to Coates et al. (Ann Rheum Dis. 2010;69: 48).Disclosure of Interests:Alen Zabotti: None declared, Michele Maria Luchetti Speakers bureau: Honorary fees for conferences and workshops by Janssen, Abbvie, Novartis, Lilly, Celgene, Pfizer, Carlo Selmi Speakers bureau: Honoraria and/or speaker bureau from AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer, Sanofi-Regeneron, Grant/research support from: Research support from Amgen, Janssen, Novartis, Pfizer, Roberta Ramonda Speakers bureau: Honoraria and speaker fees from Novartis, Abbvie, Pfizer, MSD, Janssen, Rosa Daniela Grembiale: None declared, Lorenzo Dagna Consultant of: Consultation honoraria from Abbvie, Amgen, Biogen, Celltrion, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI, Salvatore D'Angelo Speakers bureau: Consulting fees and/or speakers bureau from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi and UCB, Giacomo Cafaro: None declared, Salvatore De Vita: None declared, Mara Felicetti: None declared, Silvia Marelli Employee of: Janssen-Cilag SpA, Daniela Frigerio Employee of: Janssen-Cilag SpA, Ennio Favalli Speakers bureau: Consulting fees and/or speaking engagements from AbbVie, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Pfizer, Galapagos, Sanofi-Genzyme, and UCB

Asthma

Asthma is the most common respiratory disorder in Canada. Despite significant improvement in the diagnosis and management of this disorder, the majority of Canadians with asthma remain poorly controlled. In most patients, however, control can be achieved through the use of avoidance measures and appropriate pharmacological interventions. Inhaled corticosteroids (ICSs) represent the standard of care for the majority of patients. Combination ICS/long-acting beta2-agonists (LABA) inhalers are preferred for most adults who fail to achieve control with ICS therapy. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma, but should only be prescribed by physicians with appropriate training in allergy. Regular monitoring of asthma control, adherence to therapy and inhaler technique are also essential components of asthma management. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma

Parenchymal lung disease in adult onset Still's disease: An emergent marker of disease severity - Characterisation and predictive factors from Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort of patients

Background: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown aetiology usually affecting young adults. Interestingly, recent evidence from the juvenile counterpart of AOSD suggested the emergent high fatality rate of lung disease (LD) in these patients. In this work, we aimed to characterise LD in AOSD, to identify associated clinical features and predictive factors, and to describe long-term outcomes of the disease comparing patients with LD and those without. Methods: A retrospective assessment of prospectively followed patients, from January 2001 to December 2019, was provided to describe the rate of LD in AOSD, associated clinical features and predictive factors, and long-term outcomes. Patients with AOSD, who were included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort, were assessed. Results: Out of 147 patients included in GIRRCS cohort, 18 (12.25%) patients were reported to be affected by LD, at the time of diagnosis of AOSD, who were characterised by older age, a higher prevalence of myalgia, of lymph node involvement, of pleuritis, and abdominal pain. Furthermore, patients with LD showed higher values of systemic score and ferritin. Among those clinical variables, older age and systemic score were also independently predictors of LD. Chest CT scans were also obtained, and the most common finding was the peripheral consolidations in 8 (44.4%) patients. Finally, a higher mortality rate, of 38.9%, was registered in patients with LD than others, since it was associated with a significant decreased survival rate. Conclusions: The presence of LD could suggest an emergent cause of mortality in AOSD, as observed in juvenile counterpart recognising a further marker of severity and poor prognosis to be careful evaluated. Patients with LD were also characterised by some clinical features, higher values of systemic score and ferritin than the others, identifying a subset of patients mostly burdened by systemic signs and symptoms. Although specific designed future studies are needed to fully elucidate the significance of LD in AOSD, a more accurate evaluation and management of this feature could improve the long-term outcomes of these patients

Implementing a simple pharmacovigilance program to improve reporting of adverse events associated with biologic therapy in rheumatology: Preliminary results from the Calabria Biologics Pharmacovigilance Program (CBPP)

Introduction: Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs' reporting associated with biologics use in rheumatology. Materials and methods: We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. Results: During the study period, 399 patients (245 females; mean age: 58 \ub1 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p &lt; 0.0001). The most common AEs were injection site reactions and skin disorders. Conclusions: In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology