Safety of Janus Kinase Inhibitors: A Real-World Multicenter Retrospective Cohort Study.

OBJECTIVE: Oral Janus kinase inhibitors (JAKis) represent an effective strategy for rheumatoid arthritis (RA) treatment. A previous study supported that tofacitinib (TOF) is associated with higher incidence of cardiovascular (CV) and neoplastic events compared to tumor necrosis factor inhibitors. Given the apparent discrepancy between these data and real-world experience, we aimed to investigate the safety and efficacy of the available JAKis in a multicenter cohort. METHODS: We retrospectively evaluated patients with RA who ever received 1 JAKi (TOF, baricitinib [BAR], upadactinib [UPA], filgotinib [FIL]) from 4 tertiary care centers in Milan, Italy. Outcomes related to JAKi safety were recorded, particularly major CV events as well as adverse events of special interest (AESIs), which included serious infections, opportunistic infections, venous thromboembolism, herpes zoster infections, liver injury, malignancies, and deaths; retention rates were also calculated. Further analyses included patients fulfilling the risk factors suggested to influence TOF safety. RESULTS: Six hundred eighty-five patients were included and received BAR (48%), TOF (31%), UPA (14%), or FIL (7%) as first-line innovative treatment prior to a biologic. Of a total of 1137 patient-years of observation, we recorded 1 stroke and 123 (18%) AESIs, including 3 deaths, all a result of severe infections. Among patients with a higher CV risk, we observed a higher frequency of AESIs (23%). CONCLUSION: Our real-world data confirm that JAKis are effective and carry a low risk of AESIs, especially in patients who do not display CV risk factors at baseline. Our study could not identify differences between JAKis. Different safety profiles should be defined in larger prospective cohorts.

Joining telehealth in rheumatology: a survey on the role played by personalized experience from patients' perspective.

BACKGROUND: The beginning of the Covid-19 pandemic has forced many hospital departments worldwide to implement telehealth strategies for the first time. Telehealth represents the opportunity to increase value for all stakeholders, including patients and healthcare staff, but its success constitutes a challenge for all of them and particularly patients play a crucial role for their needed adherence. This study focuses on the experience of the Rheumatology Unit of Niguarda Hospital in Milan (Italy), where telehealth projects have been implemented for more than a decade with structured design and organized processes. The case study is paradigmatic because patients have experimented personalized mixes of telehealth channels, including e-mails and phone calls, Patient Reported Outcomes questionnaires, and home delivery of drugs. Given all these peculiarities, we decided to deepen patients' perspective through three main aspects related to the adoption of telehealth: (i) the benefits perceived, (ii) the willingness to enrol in future projects, (iii) the preference on the service-mix between remote contacts and in-person visits. Most importantly, we investigated differences in the three areas among all patients based on the mix of telehealth channels experienced. METHODS: We conducted a survey from November 2021 to January 2022, enrolling consecutively patients attending the Rheumatology Unit of Niguarda Hospital in Milan (Italy). Our survey comprised an introductory set of questions related to personal, social, clinical and ICT skills information, followed by the central part on telehealth. All the answers were analysed with descriptive statistics and regression models. RESULTS: A complete response was given by 400 patients: 283 (71%) were female, 237 (59%) were 40-64 years old, 213 (53%) of them declared to work, and the disease most represented was Rheumatoid Arthritis (144 patients, 36%). Descriptive statistics and regression results revealed that (i) non-users imagined wide-ranging benefits compared to users; (ii) other things being equal, having had a more intense experience of telehealth increased the odds of accepting to participate to future projects by 3.1 times (95% C.I. 1.04-9.25), compared to non-users; (iii) the more telehealth was experienced, the higher the willingness to substitute in-person with online contacts. CONCLUSIONS: Our study contributes to enlighten the crucial role played by the telehealth experience in determining patients' preferences.

The effect of gender on methotrexate prescription attitudes in Italian rheumatoid arthritis patients: the MARI study.

OBJECTIVES: The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy. METHODS: The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender. RESULTS: There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002). CONCLUSIONS: In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

The effect of newly diagnosed undifferentiated connective tissue disease on pregnancy outcome.

OBJECTIVE: The purpose of this study was to evaluate pregnancy outcome in a cohort of patients with newly diagnosed undifferentiated connective tissue disease (UCTD). STUDY DESIGN: We conducted a nested case-control study that compared 41 patients who had early UCTD that was diagnosed at 11-14 weeks of pregnancy with 82 healthy control subjects. RESULTS: During pregnancy, UCTD progressed to a definite connective tissue disease in 2 of 41 patients (4.9%). Sixteen of the 41 patients (39%) with UCTD tested positive for anti-Ro (SSA) antibodies. Compared with the control subjects, the women with UCTD had higher rates of small for gestational age (SGA; 12/40 vs 11/80; P = .05). The rate of complications of pregnancy (preterm delivery at

High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor alpha inhibitors in rheumatoid arthritis.

OBJECTIVE: To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor alpha (TNFalpha) inhibitors. METHODS: The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow-up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFalpha treatment and 1 year later. RESULTS: The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non-responder group (130.4 U/ml (interquartile range 13.8-276.7) v 24.8 U/ml (10.2-90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti-CCP antibody levels were not significantly affected. CONCLUSIONS: According to the clinical response, anti-TNFalpha agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFalpha inhibitors.