According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician’s preference. We ...analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into “first-” and “second-line” bDMARD. We included 1910 patients (first line
n
= 1264, second line
n
= 646). Age was higher in ABA or TCZ vs TNFi treated patients (
p
< 0.0001). Positive latent tuberculosis screening was associated with first-line ABA (
p
= 0.002). Methotrexate (MTX) combination therapy was lower in the TCZ group (
p
= 0.02). The type (dyslipidemia, hypertension, pulmonary disease) and the number of comorbidities influenced the choice towards ABA (
p
= 0.01). Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives:
Women with Rheumatoid Arthritis (RA) can experience flares during pregnancy that might influence pregnancy outcomes. We aimed at assessing the disease course during pregnancy and ...identifying risk factors for flares.
Methods:
Data about prospectively-followed pregnancies in RA were retrospectively collected before conception, during each trimester and in the post-partum period. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analysed with regard to disease flares.
Results:
Among 73 women who had a live birth, 64 (88%) were in remission/low disease activity before conception. During pregnancy, a flare occurred in 27 (37%) patients, mainly during first and second trimester. Flares during pregnancy were associated with the discontinuation of bDMARDs at positive pregnancy test (55% of patients with flare vs
.
30% of patients with no flare,
p
0.034, OR 2.857, 95% CI 1.112–8.323) and a previous use of >1 bDMARDs (33% of patients with flare vs
.
10% of patients with no flare,
p
0.019, OR 4.1, 95%CI 1.204–13.966). Preterm pregnancies were characterised by higher values of CRP 10 mg/L (5–11) vs
.
3 mg/L (2.5–5),
p
0.01 and DAS28-CRP3 4.2 (1.9–4.5) vs
.
1.9 (1.7–2.6),
p
0.01 during the first trimester as compared with pregnancies at term. Preterm delivery was associated with the occurrence of flare during pregnancy (flare 27% vs
.
no-flare 7%,
p
0.034, OR 4.625, 95%CI 1.027–20.829).
Conclusion:
Preterm delivery in RA patients was associated with flares during pregnancy. Flares occurred more frequently after the discontinuation of bDMARDs at positive pregnancy test. Women with aggressive RA on treatment with bDMARDs should be considered as candidates for continuing bDMARDs during pregnancy in order to reduce the risk of flare and adverse pregnancy outcomes.
Objectives
To evaluate the 2‐year retention rate of golimumab compared with etanercept and adalimumab as second‐line biologic agent in rheumatoid arthritis (RA) patients who failed a previous tumor ...necrosis factor inhibitor (TNFi).
Methods
Data on RA patients treated with a second‐line subcutaneous TNFi were extracted from a multicentric Italian cohort (the LORHEN registry). The analysis was limited to etanercept, adalimumab and golimumab in the period when all were available in Italy (since October 2010). The 2‐year retention rate was calculated by Kaplan–Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log‐rank test.
Results
One hundred and ninety‐five RA patients treated with etanercept (n = 76), adalimumab (n = 68) or golimumab (n = 51) were included in the analysis. The 2‐year retention rate (40% with a median time‐on‐drug of 12.9 months in the whole population) was significantly lower for adalimumab (31.2%, P = 0.018) and numerically lower for etanercept (39.8%, P = 0.068) compared with golimumab (53.4%) because of a higher discontinuation rate due to adverse events (P = 0.042 and P = 0.038 versus golimumab, respectively). Drug survival was greater in concomitant synthetic disease modifying anti‐rheumatic drug (sDMARD) users (44.2%) compared with TNFi monotherapy (22.5%, P = 0.036). No difference was found in survival analysis according to first‐line TNFi reason for discontinuation and pattern of TNFi switch (antibody‐receptor, antibody‐antibody or receptor‐antibody).
Conclusions
Our real‐life data confirmed switching to a second TNFi as a good option for treating first‐line TNFi failures in RA, especially in combination with sDMARDs. Second‐line golimumab showed an overall better 2‐year drug survival compared with adalimumab and etanercept.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this ...registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old.
RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected.
A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (
= 0.02), JAKi (
< 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (
= 0.013).
We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.
Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis and Psoriasis determine a high cost to the Italian National Health Service (INHS). The availability of biological drugs – among which ...etanercept – greatly improved treatment efficacy. The biological drugs are an expensive resource. Etanercept patent protection has expired, and biosimilar has been recently approved. Considering the perspective of the INHS, a drug budget impact (DBI) analysis was conducted to evaluate the consequences of the biosimilar availability in terms of cost containment (savings), thanks to its lower price compared to the originator’s. The DBI model expects that some patients in treatment with the originator will switch (uptake rate) to the biosimilar and that some naïve patients will directly start treatment with the biosimilar (uptake rate). Separately considering all the different diseases for which etanercept is indicated (Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis and Psoriasis), the number of patients who might potentially use the biosimilar is estimated – based on disease prevalence and incidence rates, the overall proportion of treated patients and the etanercept market share. The time horizon extends to five years. The results from the analysis show (in the base case) that the availability of the biosimilar would provide overall annual savings over €25 million to the INHS in the fifth year, while the cumulated savings in the five years period would be about €90 million.
Objective: Despite the well-established efficacy of methotrexate (MTX) in rheumatoid arthritis (RA), monotherapy is not sufficient in almost half of patients. The aim of this registry-based study was ...to detect possible predictive factors for the early failure of MTX as a first-line treatment in early RA patients.
Materials and Methods: Five-hundred and ninety RA patients beginning MTX as the first-line treatment were included. Persistence on therapy was re-evaluated after 12 months. Baseline features of disease were evaluated by means of univariate Cox regression, and parameters significantly associated to the outcome were included in multivariate model.
Results: One hundred and forty-nine patients (25.3%) failed MTX during the 1st year, for inefficacy in 43.6% and adverse events in 37.5% of cases, respectively. At univariate analysis, patients who discontinued or failed treatment showed lower mean age, higher prevalence of anti-citrullinated peptide antibodies (ACPAs), and higher number of tender/swollen joints. The dose of MTX was correlated with the efficacy and the tolerance of the drug. In particular, patients treated with 7.5 mg of MTX weekly showed a higher rate of discontinuation for inefficacy than adverse events, and the contrary was detected for higher doses. On multivariate analysis, age, ACPA, and number of tender joints were directly associated with MTX discontinuation or failure.
Conclusions: More than 25% of RA patients treated with MTX as a first-line therapy failed treatment at 12 months. ACPA positivity, age, and number of tender joints were associated with early withdrawal of MTX in RA patients, while the dose of MTX was correlated to the efficacy and safety of the drug.
Objective
Obesity is a mild, long‐lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity ...represents a risk factor for a poor remission rate in RA patients requiring anti–tumor necrosis factor α (anti‐TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease‐modifying antirheumatic drugs.
Methods
Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as <25, 25–30, and >30 kg/m2), acute‐phase reactants, IgM rheumatoid factor, and anti–cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of <2.6 lasting for at least 3 months.
Results
Six hundred forty‐one outpatients with longstanding RA receiving anti‐TNFα blockers (adalimumab, n = 260; etanercept, n = 227; infliximab, n = 154), recruited from 2006–2009 and monitored for at least 12 months, were analyzed. The mean ± SD DAS28 at baseline was 5.6 ± 1.4. A BMI of >30 kg/m2 was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti‐TNFα treatment, a DAS28 of <2.6 was noted in 15.2% of the obese subjects, in 30.4% of the patients with a BMI of 25–30 kg/m2, and in 32.9% of the patients with a BMI of <25 kg/m2 (P = 0.01). The lowest percentage of remission, which was statistically significant versus adalimumab and etanercept (P = 0.003), was observed with infliximab.
Conclusion
Obesity represents a risk factor for a poor remission rate in patients with longstanding RA treated with anti‐TNFα agents. A personalized treatment plan might be a possible solution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The observational RAPSODIA (RA, PsA and spondylitis including AS) study was planned to assess, in patients with RA, AS and PsA, their involvement in medical decisions, quality of life and unmet needs ...15 years after the introduction of biologic therapies in Italy.
Patients completed a questionnaire during their scheduled rheumatology consultation. They rated their satisfaction with disease knowledge on a 5-point scale (1 = not at all satisfied, 5 = totally satisfied). Self-efficacy, defined as judgement of one's own ability to achieve given levels of performance and exercise control over events, was measured using the pain subscale of the Arthritis Self-Efficacy Scale. Patients' global assessments of pain, fatigue and disease activity were recorded on 100 mm visual analogue scales (0 = best status, 100 = worse status). Disease activity status was assessed using standard tools. Health status was measured using the 36-item Short Form Health Survey and the Italian version of the HAQ.
Ninety-eight per cent of patients reported that their health care practitioner used understandable terms to explain their condition. Joint issues and general symptoms (e.g. fatigue and malaise) were common. All measures of disease activity and self-efficacy scores were markedly better in patients receiving biologic vs conventional therapy. Biologic therapy recipients were more productive at work.
These results confirm that some patients with rheumatic diseases are not satisfied with the level of information they receive about their treatments. Biologic therapy appears to be an important advance, with patients receiving this form of treatment having improved symptoms and productivity. However, patients still report unmet needs. Thus further research, and perhaps new and more effective therapies, along with better education and multidisciplinary collaboration, are required to improve outcomes.
A cohort of rheumatoid arthritis (RA) patients in the Lombardy Rheumatology Network (LOHREN) registry and receiving anti‐TNF therapy was evaluated after 6, 12, 24, and 36 months. Of the 1114 patients ...in the registry 1064 met the clinical criteria for inclusion with 519 receiving infliximab, 303 adalimumab, and 242 etanercept. The therapeutic survival curve of these patients showed that the likelihood of continuing anti‐TNF therapy was 78.8% after 12 months, 65.2% after 24 months, and 52.9% after 36 months, with a risk of dropout similar for inefficacy and adverse events. There were 405 anti‐TNF therapy discontinuations (38.1%): 180 (16.9%) due to inefficacy, 194 (18.2%) adverse events, and 31 (2.9%) other reasons. Four deaths (2 septicemia, 1 postinfective cerebritis, 1 heart failure) were considered to be related to anti‐TNF therapy. Of the discontinuations, 219 (54.1%) occurred within the first 12 months: 110 due to adverse events, 89 inefficacy, and 20 due to other reasons. After 36 months, the likelihood of survival on etanercept (62.5%) was significantly greater than the likelihood of survival on infliximab (49.1%) or adalimumab (53.6%). A higher risk of therapy discontinuations due to adverse events was associated with increasing age, a corticosteroid >5 mg/day, a high erythrocyte sedimentation rate (ESR), a higher risk of therapy discontinuations due to inefficacy was associated with the previous use of ≥4 disease‐modifying antirheumatic drugs (DMARDs) and a high ESR. Comorbidities, increasing DAS28 values and co‐therapy with methotrexate were associated with a lower risk of discontinuation.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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