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.

Effective Desensitization to Tocilizumab in Delayed Hypersensitivity Reaction.

We present tocilizumab desensitization of a 47-year-old woman affected by rheumatoid arthritis with full body delayed erythematous urticarial reaction. Skin test for tocilizumab gave cutaneous reaction after 6 h at 20 mg/mL. The schedule of desensitization was then adapted for non-immediate reaction. We prepared a desensitization procedure reaching the cumulative dose of 516 mg in 5 weeks. After 6 months, the repetition of skin tests had a negative result, with demonstration of tolerance induction. Today the patient has good control of the disease.

Does early arthritis clinic organisation improve outcomes? What evidence is there? A systematic review.

OBJECTIVES: To perform a systematic review aimed to identify studies addressing the effect of the establishment of a structured organisation programme, named early arthritis clinic (EAC), finalized to manage patients with early arthritis (EA) or suspected early rheumatoid arthritis (ERA). METHODS: A literature search was performed until May 2012 using electronic databases. Additional information was obtained through a hand and grey literature search. Primary and secondary outcomes and eligibility criteria have been defined. RESULTS: The search provided a total of 3367 citations and, after the selection process, 11 non randomised controlled trials were selected, including a total of 8240 participants. The efficacy of EAC did clearly emerge with regard to reduction of the referral lag time and of the time to treatment (secondary outcomes). Only two studies met the primary outcomes: one study demonstrated that the EAC contributed to reducing disease activity and radiographic progression but not functional disability, while another reported a reduction of pain after a 6-12-month period of follow-up. CONCLUSIONS: Whether the establishment of EAC would improve the prognosis of EA in terms of primary outcomes such as clinical, functional and radiologic progression compared to patients managed outside from EAC does appear a still poorly addressed issue in the literature, which should be recognised as an urgent unmet need by the rheumatology community to gain more evidence-based information on this topic.

Residual inflammation in psoriatic arthritis patients in stable minimal disease activity.

Background: In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA. Methods: In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18-6 and 13-5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests. Results: The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6-65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively. Conclusions: PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination.

[Methodological problems associated with the planning of.]. / Problematiche metodologiche nella pianificazione e nel calcolo della dimensione del campione di un cluster randomized trial (CRT): il caso del Progetto Raffaello.

Cluster randomization, where groups (or clusters) of subjects, rather than single individuals, are randomly allocated to intervention groups, is increasingly being adopted in studies to evaluate interventions directed at a whole area or healthcare unit (such as a hospital ward, or a medical practice). Studies that use this method of randomization are referred to as cluster randomized trials (CRT) and have considerable organizational and economic advantages. However, CRTs have distinctive ethical issues that need to be considered and most importantly, require a series of methodological modifications during data analysis and calculation of sample size (during which additional parameters, such as the intracluster correlation coefficient and the design effect, need to be obtained). Methodological guidelines for conducting CRTs have been published in November 2002. However, no scientific articles dealing with the methodology associated with the design and analysis of this type of study have yet been published in Italian. The aim of this article, therefore, is to provide methodological support to healthcare researchers who are planning a CRT, through a description of the methodology used in the Raffaello project. This project is in the start-off phase in the Marche and Abruzzo regions of Italy and represents an excellent case study, it being a CRT aimed at evaluating the efficacy of a Disease Management model in the general population (with general practitioners therefore, being the cluster of randomization).

Aromatase inhibitors and anti-synthetase syndrome.

Adjuvant therapy in postmenopausal women with endocrine-responsive breast cancer (BC) is actually centered on the use of anti-aromatase inhibitors (AI). Several reports, however, are emerging in literature associating the use of this drugs to rheumatic disorders. This case report describes the first case of anti-synthetase syndrome diagnosis after treatment with anti-estrogen agents in a patient with pre-existing rheumatoid arthritis.