Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients.

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan-Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07-1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study.

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.

Reliability and validity of the Italian version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument in patients with systemic sclerosis.

OBJECTIVES: To test the acceptability, feasibility, reliability and validity of the Italian translated version of the UCLA Scleroderma Clinical Trial Consortium GIT (UCLA-SCTC GIT) 2.0. Gastrointestinal tract (GIT) involvement is frequent in systemic sclerosis (SSc). The UCLA-SCTC GIT 2.0 is a validated instrument for measuring the presence and impact of GIT symptoms in SSc patients. METHODS: Acceptability and feasibility of the questionnaire were evaluated based on the input from the patients. Internal consistency was evaluated by Cronbach's alpha. External consistency was measured by comparing with the Short Form (SF)-36 and EQ-5D by Spearman's rho, meaningful if ≥0.30. RESULTS: Sixty-two consecutive SSc patients (mean age 60.6) were recruited, 88.5% were female. The UCLA-SCTC GIT 2.0 was well accepted. Percentage of missing data in UCLA-SCTC GIT total score was 2 %. Internal consistency was acceptable (alpha≥0.70) for all domains. Cronbach's alpha was ≥0.70 for all domains. UCLA-SCTC GIT 2.0 discriminated between patients with or without gastroesophageal reflux disease whether diagnosed clinically or by objective testing (p<0.01 for both). UCLA-SCTC GIT emotional well-being was correlated with the conceptually equivalent SF-36 mental health domains (correlation coefficient>0.35) and with the EQ-5D usual activities domain (0.38), thus reflecting the impact on everyday activities. The distention/bloating domain strongly correlated with the EQ-5D anxiety/depression domain (0.51) and reflux domain with role emotional of SF-36 (0.44). CONCLUSIONS: This is the first validation study of the Italian version of UCLA-SCTC GIT 2.0. Our data support its feasibility, reliability, and validity in Italian SSc patients.

Infliximab treatment in psoriatic arthritis: our experience.

The aim of this work was to give clinical practice recommendations on the use of tumour necrosis factor blocking agents in psoriatic arthritis, underlining the pathogenetic mechanism of this condition and its articular and dermatologic manifestations. We retrace the stages leading to the therapeutic indications of biological agents that are presently used in the treatment of psoriatic arthritis: Entanercept, Adalimumab, Infliximab. We also report our personal experience describing an emblematic case of a patient with psoriatic arthritis in which a decisive regression of joint/skin involvement was obtained with Infliximab treatment.

Effects of urine dilution on quantity, size and aggregation of calcium oxalate crystals induced in vitro by an oxalate load.

Increasing urinary volume is an important tool in the prevention of calcium renal stones. However, the mechanism of how it actually works is only partially understood. This study aimed at assessing how urine dilution affects urinary calcium oxalate crystallization. A total of 16 male idiopathic calcium oxalate (CaOx) stone-formers and 12 normal male subjects were studied and 4 h urine samples were taken twice, under low (undiluted urine) and high hydration conditions (diluted urine). An equal oxalate load (1.3 mmol/L) was added to both types of urine and the crystallization parameters were assessed. In both stone-formers and normal subjects, the crystallization processes were significantly (p<0.05 or less) more marked in the undiluted urine than in the diluted urine in terms of: a) total quantity of calcium oxalate dihydrate (COD) and calcium oxalate monohydrate (COM) crystals; b) total quantity of crystalline aggregates; and c) aggregation index (i.e., ratio between the area occupied by crystalline aggregates and the area occupied by all the crystals present). The comparison between stone-formers and normal subjects showed that the greatest difference was for the size of COD crystals, which were larger in the urine of the stone-formers. A further important finding was an inverse relationship between changes in urinary volume and in the aggregation index (r = -0.53, p = 0.004). In conclusion, urine dilution considerably reduces crystallization phenomena induced in vitro by an oxalate load in both calcium stone-formers and normal subjects.

The effect of fruits and vegetables on urinary stone risk factors.

BACKGROUND: The overall effect of fruit and vegetable intake on urinary stone risk profile is not yet known. METHODS: We studied the effect of a two-week period of fruit and vegetable elimination on urinary stone risk profile in 12 normal adults, and of supplementing the diet with a fair quantity of low-oxalate fruits and vegetables in 26 idiopathic calcium stone formers characterized by hypocitraturia and a very low fruit and vegetable intake in their usual diet. RESULTS: In the normal subjects, the elimination of fruits and vegetables from the diet decreased the urinary excretion of potassium (-62%), magnesium (-26%), citrate (-44%) and oxalate (-31%), and increased that of calcium (+49%) and ammonium (+12%) (P < 0.05 for all). The relative saturation for calcium oxalate and calcium phosphate increased from 6.33 to 8.24 (P = 0.028), and from 0.68 to 1.58 (P = 0.050), respectively. In the hypocitraturic stone formers, the introduction of these foods in the diet increased urinary volume (+64%), pH (from 5.84 to 6.19), excretion of potassium (+68%), magnesium (+23%), and citrate (+68%), while it decreased the excretion of ammonium (-18%) (P < 0.05 for all). The relative saturation for calcium oxalate and uric acid fell from 10.17 to 4.96 (P < 0.001), and from 2.78 to 1.12 (P = 0.003), respectively. CONCLUSION: The total elimination of fruits and vegetables in normal subjects brings about adverse changes in the urinary stone risk profile that are only partially counterbalanced by a reduction in oxalate. In contrast, the addition of these foods to the diet of hypocitraturic stone formers not used to eating them not only significantly increases citrate excretion without affecting oxalate excretion, but also decreases calcium oxalate and uric acid relative saturation.

[Analysis of the problem of "difficult hospital discharges" in the University Hospital of Parma]. / Analisi del problema "dimissioni difficili" nell'Azienda Ospedaliera-Universitaria di Parma.

We analyzed, in a middle-sized hospital, the problems related to the so-called "difficult discharges", conceived as situations involving an economic, human and organizational burden exceeding patients' and their families' capacities and requiring a specific involvement of territorial services. During a whole year (July 1, 2001-June 30, 2002) the cases found were 591. We demonstrated that the problem concerns mainly elderly patients, almost equally distributed between males and females, a quarter of the sample being represented by patients who had recently undergone surgery and whose discharge difficulties were mostly related to mixed social and sanitary problems. This kind of patients is faced with long-term hospitalization implicating a large number of intra-hospital transfers due to the presence of severe and disabling pathologies, mainly neoplasms and strokes, often associated with other serious diseases, various complications and difficult situations from the health point of view. About half of the patients had the possibility to go back home, while the rest required lodging in territorial structures such as nursing homes and retirement homes. The average time-lapse between the possible discharge indicated by the hospital physician and the actual discharge was 10 days, with global annual 6106 days of "improper" hospitalization. Our conclusion is that the phenomenon of difficult discharges is nowadays a very topical problem and that it should be faced with a new model of continuous and integrated assistance organization.

Body weight, diet and water intake in preventing stone disease.

Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature.

Calcium oxalate crystallization in untreated urine, centrifuged and filtered urine and ultrafiltered urine.

Centrifuged and filtered urine is often used to evaluate in vitro the crystallization processes of calcium oxalate (CaOx), but even such simple manipulations can alter the composition of the urine, as regards its protein and lipid concentrations. In urine samples taken from 17 normal male adults, we evaluated CaOx crystallization by simultaneously using three different types of urine: untreated (U), centrifuged at 2000 rpm (800 g) and filtered at 0.22 microm (CF), and centrifuged-filtered and ultrafiltered at 10 000 Da (CFU). The addition of 1.2 mmol/l of oxalate to each type of urine produced notably different results. The total amount of CaOx crystals (expressed as calcium oxalate dihydrate crystals (COD) + oxalate monohydrate crystals (COM) area/total area x 100) was on average 13.2% in U urine, 70.7% in CF urine and 11.1% in CFU urine (CF > U and CFU, U = CFU); the relative prevalence of COD and COM (expressed as COD area/COM area) was on average 71.4 in U urine, 0.0026 in CF urine and 5.5 in CFU urine (U > CF and CFU, CFU > CF); the diameter of COD (expressed in microns) was on average 15.2 in U urine, 3.7 in CF urine and 24.3 in CFU urine (CFU > U and CF, U > CF); the diameter of COM (expressed in microns) was on average 5.2 in U urine, 2.6 in CF urine and 8.9 in CFU urine (CFU > U and CF, U > CF); the total amount of CaOx aggregates (expressed as CaOxAgg area/total area x 100) was on average 8.5% in U urine, 22.1% in CF urine and 2.9% in CFU urine (CF > U and CFU, U > CF). We conclude that CaOx crystallization processes in manipulated urine are extremely different, probably due to changes in macromolecular compounds.