Long-term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen.

Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ± 12.3 years) treated with iloprost for 7.1 ± 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/kg/min). In all patients, modified Rodnan skin score (4.7 ± 5.3 vs. 3.7 ± 5.3, p < 0.0001), systolic pulmonary arterial pressure (sPAP) (30.9 ± 6.4 vs. 24.0 ± 3.2 mmHg, p < 0.0001), tricuspid annular plane systolic excursion (22.1 ± 2.4 vs. 23.8 ± 3.5 mm, p = 0.0001), pro-brain natriuretic peptide (97.2 ± 69.3 vs. 65.8 ± 31.7 pg/ml, p = 0.0005) showed statistically significant improvement from baseline. In the subgroup of patients with baseline sPAP ≥36 mmHg (n = 17), a significant sPAP reduction was observed (from 39.5 ± 3.8 to 25.1 ± 4.5 mmHg, p < 0.0001) after 7.6 ± 2.5 years of follow-up. The number of patients with digital ulcers (DUs) at follow-up was reduced from baseline (42.6 vs. 11.8%, p < 0.001), and none of the free-DU patients at baseline presented DUs at follow-up. An intensive and chronic regimen of IV iloprost administration seems to stabilize and potentially improve the long-term development of disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy.

Tailored first-line biologic therapy in patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis.

OBJECTIVE: A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs. RESULTS: Some variables, including the patients' preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or UTK choice is guided by skin or articular disease severity, enthesitis, and dactylitis, whereas ETN should be preferred if metabolic syndrome or high CV risk complicate PsA. CONCLUSION: Taking in account of multiple choice driving variables, first-line biologic therapy may be optimized in patients with RA, SpA, and PsA.

Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, to whose pathogenesis neoplastic and immune-mediated mechanisms contribute. Mammalian target of rapamycin (mTOR)-inhibitors have antiproliferative and immunosuppressive properties. We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. PDN was given initially at 0.75 mg/kg per day, tapered to 5 to 2.5 mg per day by month 6. Target SRL blood levels were 8 to 12 ng/mL. Treatment was continued for at least 24 months in patients who showed disease stabilization or improvement. Ten patients were enrolled; 8 achieved stable disease or objective responses, whereas 2 had disease progression. Responses were mainly observed at the following sites: retroperitoneum in 5/8 patients (62.5%), cardiovascular in 3/4 (75%), bone in 3/9 (33.3%), and central nervous system (CNS) in 1/3 (33.3%). The median follow-up was 29 months (interquartile range, 16.5-74.5); 2 patients died of progressive CNS disease and small-cell lung cancer, respectively. Treatment-related toxicity was mild. Using immunohistochemistry and immunofluorescence on ECD biopsies, we detected expression in foamy histiocytes of the phosphorylated forms of mTOR and of its downstream kinase p70S6K, which indicated mTOR pathway activation. In conclusion, SRL and PDN often induce objective responses or disease stabilization and may represent a valid treatment of ECD. The trial is registered at the Australia-New Zealand Clinical Trial Registry as #ACTRN12613001321730.

Arterial stiffness is increased in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low-grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. METHODS: Thirty-two IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19-49 years). SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure carotid-femoral and carotid-radial (muscular artery) pulse wave velocity (PWV), augmentation index and central blood pressure. RESULTS: Carotid-femoral PWV was higher in IBD patients than in controls (6.6 ±â€Š1.4 vs. 6.0 ±â€Š0.8 m/s, respectively, P < 0.05), as well as carotid-radial PWV (8.5 ±â€Š1.2 vs. 7.2 ±â€Š1.0 m/s, P < 0.001). Central pulse pressure was higher in IBD than in controls (32 ±â€Š6 vs. 28 ±â€Š7 mmHg, P < 0.05). Aging was an important determinant of carotid-femoral PWV in both groups and carotid-radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid-femoral PWV [R(2) = 0.10; +0.05 m/s per 1 year of aging, 95% confidence interval (CI) 0.01-0.08 m/s, P < 0.05], as well as IBD (R(2) = 0.10; +0.72 m/s if IBD present, 95% CI 0.19-1.26 m/s, P < 0.05). In IBD patients, carotid-radial PWV was positively associated with the disease duration (R(2) = 0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03-0.19 m/s, P < 0.05). CONCLUSION: Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.