Explore the vast range of titles available.

Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G 1 cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the in vivo efficacy of CPI-0610 in a MM xenograft mouse model. Our study found IKZF1 and IRF4 to be among the primary targets of CPI-0610, along with MYC . Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show in vitro synergism, in part due to concomitant suppression of IKZF1 , IRF4 and MYC , providing a rationale for clinical testing of this drug combination in MM patients.

Background:There is emerging evidence that chronic arthritis, namely psoriatic arthritis (PsA), spondylarthritis (SpA) and rheumatoid arthritis (RA) have a different disease course upon sex difference, but whether hormonal status may impact on drug effectiveness has been scarcely investigated.Objectives:To compare the effectiveness of certolizumab on clinical outcomes in female patients with PsA, SpA, and RA starting the therapy during fertility or menopause age.Methods:We analyzed the charts of patients affected with PsA, SpA, and RA from the Apulian BIOPURE registry starting a treatment with certolizumab from January 2016 to May 2023. Female patients were divided upon their hormonal status. A cohort of male patients was analyzed as reference cohort. Descriptive statistics (mean, SD, or percentages) were performed for demographic (age, BMI, comorbidities) and disease related characteristics (disease duration, DAS28, DAPSA, ASDAS-CRP, HAQ, VAS-pain, Pts-GA, glucocorticoids, cDMARDs) at baseline, 12 months and at last observation. Drug survival was evaluated by Kaplan-Meier life table analysis, and differences were tested with the log-rank test. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation adjusted for patient’s demographics, disease characteristics, hormonal status, and prior biologic treatments were computed by multivariate regression models. The achievement of low disease activity (LDA) was assessed at 12 months and the difference between fertile and menopausal females was compared by chi-square test.Results:We recruited n.542 patients starting certolizumab in the time frame of the study, of whom n. 240 had PsA, n. 185 SpA, and 117 were diagnosed with RA. Of n.413 females, n.202 were on fertile age and n. 211 on menopause at beginning of treatment with certolizumab. N.129 were males. Baseline demographic and clinical characteristics, and the comparison between fertile and menopausal age are shown on detail in Table 1. No significant difference of drug survival rates was observed between female on fertile age (63%, median 55.4 months) and those on menopause (57%, median 53.5 months). No difference in terms of drug persistence was also found within each disease (Figure 1). At 12 months, LDA based on DAS28 was achieved in 86% of fertile and 59% of menopausal female (p<0.0001); while DAPSA based LDA was obtained 85% of fertile and 69% of menopausal female (p<0.002). Logistic multiple regression analysis showed that the only baseline covariates associated to drug discontinuation were the lack of glucocorticoid (negative predictor OR 0.60, 95 % CI 0.39-0.91) and biologic-naïve patients (negative predictor OR 0.57, 95 % CI 0.34-0.96), while the fertility/menopause age did not.Conclusion:In real-life settings, the hormonal status does not affect the drug persistence of certolizumab in female with chronic arthritis, although 12 months LDA was achieved more frequently in females in fertile age.Figure 1.Table 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Bed bugs have become a common urban pest with consequences on human health and economic costs to the hotel and tourism sectors. Insecticide resistance is considered an important factor in the current bed bug resurgence, and multiple resistance mechanisms could be working in the resistant bed bug populations. In the present study, we determined the resistance profile to four insecticides with a different mode of action in Cimex lectularius L. (Heteroptera: Cimicidae) field-collected colonies from Argentina. Furthermore, the synergism effect of piperonyl butoxide (PBO) with deltamethrin was investigated to explore the contribution of detoxification metabolism to resistance. Our results showed that most of the field-collected colonies are extremely resistant to deltamethrin and propoxur, much more than to azametiphos and imidacloprid. The differences in resistance ratios among field-collected colonies could be associated with different modes of action of insecticides used in control pest and the mechanisms involved in the resistance. PBO pretreatment led to a significantly decreased RR in pyrethroid-resistant colonies, suggesting an upturn of monooxygenase activity for deltamethrin detoxification. However, the high RR detected could involve other mechanisms as part of the whole resistant phenotype in colonies of C. lectularius resistant to pyrethroids.

Rapid reinfestation of insecticide-treated dwellings hamper the sustained elimination of Triatoma infestans, the main vector of Chagas disease in the Gran Chaco region. We conducted a seven-year longitudinal study including community-wide spraying with pyrethroid insecticides combined with periodic vector surveillance to investigate the house reinfestation process in connection with baseline pyrethroid resistance, housing quality and household mobility in a rural section of Pampa del Indio mainly inhabited by deprived indigenous people (Qom). Despite evidence of moderate pyrethroid resistance in local T. infestans populations, house infestation dropped from 31.9% at baseline to 0.7% at 10 months post-spraying (MPS), with no triatomine found at 59 and 78 MPS. Household-based surveillance corroborated the rare occurrence of T. infestans and the house invasion of other four triatomine species. The annual rates of loss of initially occupied houses and of household mobility were high (4.6-8.0%). Housing improvements did not translate into a significant reduction of mud-walled houses and refuges for triatomines because most households kept the former dwelling or built new ones with mud walls. Our results refute the assumption that vector control actions performed in marginalized communities of the Gran Chaco are doomed to fail. The larger-than-expected impacts of the intervention program were likely associated with the combined effects of high-coverage, professional insecticide spraying followed by systematic vector surveillance-and-response, broad geographic coverage creating a buffer zone, frequent housing replacement and residential mobility. The dynamical interactions among housing quality, mobility and insecticide-based control largely affect the chances of vector elimination.

BackgroundNowadays, rheumatoid arthritis (RA) patients can benefit from several drugs classified as biologic (b) or JAK inhibitors (JAKi). Four JAKi are now available, whose two JAKi, with predominantly JAK1 selectivity (JAK1i), came onto the market in 2020.ObjectivesThe aim of this study was to compare the effectiveness among RA patients included in BIOPURE registry on treatment on TNF inhibitors (TNFi) JAK1i, other JAKi (oJAKi), and other mechanisms of action (oMOA) bDMARD.MethodsData of RA patients who started a new line of treatment with a b/tsDMARD were prospectively collected from October 2020, when JAK1i was first prescribed, to May 2022. Demographics and disease characteristics were evaluated using standard descriptive statistics. Patients were divided in four groups: patients on TNFi therapy, patients on JAK1i (upadacitinib and filgotinib), patients on oJAKi (tofacitinib and baricitinib) and patients on oMOA (abatacept, tocilizumab and sarilumab). The drug survival was evaluated by Kaplan– Meier analysis. Estimated hazard ratios (HRs) of discontinuing therapy were assessed by multivariate regression models.ResultsSince October 2020, 580 RA patients started a new line treatment with b/tsDMARDs (171 TNFi, 192 oMOA, 88 oJAKi and 120 JAK1i). Overall cohort characteristics are reported in Table 1. As expected, monotherapy was more used in patients treated with JAK1i (73.6%), oJAKi (63.6%) and oMOA (54.7%) compared to TNFi (30.4%). Patients treated with JAK1i and oJAKi were more likely to be refractory to previous b/tsDMARDs, 76% of JAK1i and 76.2% of oJAKi had received prior treatment with ≥2 bDMARDs or other tsDMARDs. Patients treated with JAK1i presented higher disease activity compared to other b/tsDMARD and higher grade of disability at baseline compared to TNFi. Drug survival was similar between the four groups, being 66.7% for TNFi, 71.9% for oMOA, 64.8% for oJAKi and 69.8% for JAK1i (log-rank test:4.69, p=0.19) (Figure 1a). Multivariate cox regression model and K-M analysis (Figure 1b) showed that the main predictor of b/tsDMARDs discontinuation was a previous treatment with >2 b/tsDMARDs (HR: 1.85, 95% CI 1.21-2.85)Finally, a comparable number of adverse events causing drug discontinuation was observed: 10 (5.8%) in TNFi, 12 (6.3%) in oMOA, 9 (10.2%) in oJAKi and 10 (8.3%) in JAK1i.Table 1.Characteristics of RA patients treated with b/tsDMARDsVariablesTNFi (171 pt.)Other MOA (192 pt.) (84 ABA, 88 TCZ, 20 sarilumab)Prevalent JAK1i (129 pt.) (78 upadacitinib, 51 filgotinib)Other JAKi (88 pt.) (55 baricitinib, 33 tofacitinib)Age, mean (SD)56 (13)58 (12)55 (12)58 (11)Female, n(%)143 (83.6)156 (81.3)114 (88.4)71 (80.7)Seropositivity, n. (%)108 (74)123 (81.5)100 (90.9)*^50 (67.6)Erosive arthritis80 (46.8)99 (51.6)69 (53.5)48 (54.5)Comorbidities count, median (IQR)0 (0-1)1 (0-2)*1 (0-2)*0 (0-2)csDMARD, n. (%)119 (69.6)87 (45.3)*34 (26.4)*32 (36.4)*°Glucocorticoid, n. (%)99 (57.9)132 (68.8)87 (67.4)55 (62.5)Glucocorticoid dose daily, mean (SD)5.9 (3.3)6.2 (4.0)6.2 (3.9)5.5 (2.0)Biologic line, n. (%)12other99 (57.9)29 (17)43 (25.1)83 (43.2)*34 (17.7)75 (39.1)*31 (24)*°32 (24.8)66 (51.2)*21 (23.9)*°16 (18.2)51 (58)*°DAS28-ESR, mean (SD)4.2 (1.3)4.1 (1.5)4.5 (1.5)°^4 (1.2)CDAI, mean (SD)17 (10)18 (11)20 (12)^16 (8)VAS-pain, mean (SD)56 (25)53 (24)61 (25)57 (26)VAS-phGA, mean (SD)35 (18)41 (22)44 (22)*37 (22)VAS-pGA, mean (SD)56 (23)55 (24)61 (22)56 (21)HAQ-DI, mean (SD)1 (0.7)1.3 (0.8)*1.3 (0.7)*1.1 (0.8)phGA: physician global assessment; pGA: patient global assessment; VAS: visual analogue scale*p<0.05 vs TNFi; °p<0.05 vs other MOA, ^p<0.05 vs other JAKiConclusionOur study highlighted good effectiveness and safety of new and old b/tsDMARDs in Apulian cohort of RA patients included in BIOPURE registry. Of note, despite more than half patients starting JAK1i or oJAKi were multi-failure, they showed a similar drug survival compared to those on TNFi who were predominantly biologic-naïve.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Synthetic insecticides have been used for a long time as one of the most effective tools for insect pest control. However, the re-emergence of insect pests and their fast development of resistance, as has occurred for pyrethroid-resistant bed bugs Cimex lectularius L., make it necessary to develop new and safe strategies for effective pest control. This has fostered the research on new eco-sustainable formulations based on essential oils, which allows reducing the impact associated with the intensive use of synthetic insecticides on the environment and their effects on human health. This research explores the stability of water/eugenol/ethanol surfactantless emulsions loaded with imidacloprid (0.003 wt%), and their toxicity against a resistant bed bug strain. The results have shown that these emulsions enable the solubilization of a poorly water-soluble drug, such as the imidacloprid, without any significant modification of their stability. Furthermore, the application of the obtained formulations against the pyrethroid-resistant bed bug results in mortality in the 50–85% range upon topical and spray applications, with the increase of the eugenol content enhancing the effectiveness of the formulations. It may be expected that the ternary water/eugenol/ethanol mixtures could be further developed in the preparation of ready to use formulations, enabling the dispersion of insecticides for pest control.

Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1α) is a pro-inflammatory chemokine, levels of which in the MM microenvironment correlate with osteolytic lesions and tumor burden. CCL3 and its receptors, CCR1 and CCR5, contribute to the development of bone disease in MM by supporting tumor growth and regulating osteoclast (OC) differentiation. In this study, we identify inhibition of osteoblast (OB) function as an additional pathogenic mechanism in CCL3-induced bone disease. MM-derived and exogenous CCL3 represses mineralization and osteocalcin production by primary human bone marrow stromal cells and HS27A cells. Our results suggest that CCL3 effects on OBs are mediated by ERK activation and subsequent downregulation of the osteogenic transcription factor osterix. CCR1 inhibition reduced ERK phosphorylation and restored both osterix and osteocalcin expression in the presence of CCL3. Finally, treating SCID-hu mice with a small molecule CCR1 inhibitor suggests an upregulation of osteocalcin expression along with OC downregulation. Our results show that CCL3, in addition to its known catabolic activity, reduces bone formation by inhibiting OB function, and therefore contributes to OB/OC uncoupling in MM.

Background:Counseling plays a fundamental role in women affected by rheumatic diseases (RMDs) to ensure the best possible outcomes and should be started as early as possible.Objectives:The study aims to give an overview about the management of family counseling in women affected by RMDs in ItalyMethods:Nineteen Italian centers were involved. Women of childbearing age (18 to 50 years) affected by RMDs were included. Data about diagnosis, disease activity, treatment were collected during routine visits. Information about family planning was obtained through a survey including 19 questions. Data were collected from December 2021 to March 2022 and from October to December 2022.Answers from questionnaires collected from women were expressed by absolute numbers and percentage for categorical variables and mean ± deviation standard for continuous variables.To compare the groups in case of categorical variables the Chi square test was used or the Exact Fisher test when there was a limited amount of data. For continuous variables, the Student’s T test was used.Statistical significance was defined as a p value < 0.05.Results:We collected data on 560 patients, mean age 34.2 ± 5.9 years, with a mean disease duration of 8.8 ± 7.6 years. Diagnoses are summarized in Table 1.Three hundred and fifty-four patients (63%) were at their first counseling, while 112 (20%) were already receiving regular counseling. In 22.7% of cases examination was conducted with another specialist, mostly represented by the gynecologist (89.8%).Fifty percent of patients were treated with conventional synthetic disease modifying antirheumatic drugs (DMARDs), with hydroxychloroquine being the most frequently used (30%), while a smaller percentage of patients received biologic DMARDs (39.6%), mostly represented by TNF inhibitors (29.6%). Only 1.8% of patients were treated with JAK inhibitors.At the time of assessment, 135 of patients were planning a pregnancy, 162 were pregnant and 246 were actively avoiding pregnancy. Two hundred-forty-one patients (43%) reported to use a contraceptive method: barrier method in 69%, estroprogestinic in 18% and intra-uterine device in 2.5%; 319 (57%) were not using any contraception. Within this group, 17% were taking medications incompatible with pregnancy.Most patients (72%) were aware of the effects of their disease on pregnancy but only 53% knew about disease impact on the newborn; 74% of patients showed knowledge about the effect of drugs on pregnancy, 59% were aware of the effects of medications on newborns and 40% understood the long-term effects of therapy on their children.Patients who repeatedly underwent counseling over time had a significantly higher awareness of the disease impact on pregnancy and newborns and of the effects of drug therapy on themselves and their infants in both the short and long term. Answers in the two groups are shown in Table 2.Conclusion:This study demonstrates that a high percentage of patients knows the impact of RMD on pregnancy and vice-versa but a lack of knowledge about the effects of therapies on the newborn has emerged and need to be improved. It also demonstrates the importance to repeat counseling over time to improve patients’ empowerment. An effort should be made in informing patients about the risk of the lack of contraception or the use of less effective method of contraception, especially in those undergoing treatment incompatible with pregnancy.REFERENCES: NIL.Acknowledgements:NIL.Disclosure of Interests:Giulia Carrea: None declared, Maria Gerosa UCB, Astrazeneca, Marta Mosca UCB (Advisor), Melissa Padovan: None declared, Sabrina Paolino: None declared, Maria Grazia Anelli: None declared, Roberta Ramonda: None declared, Cecilia Nalli: None declared, Patrizia Rovere-Querini: None declared, Elisa Bellis: None declared, Salvatore D’Angelo: None declared, Enrico Fusaro: None declared, Maria Sole Chimenti Maria Sole Chimenti has received speaker honoraria and/or unrestrictive research grants from Ely, Lilly, Abbvie, Pfizer, UCB, Novartis, Janssen, Leonardo Santo: None declared, Marco Gabini: None declared, Giulia Pazzola: None declared, Francesca Serale: None declared, Carlomaurizio Montecucco: None declared, Fabrizio Conti: None declared, Roberto F. Caporali: None declared.

BackgroundIn the age of targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDs), filgotinib represents the last JAK inhibitor available in Europe for rheumatoid arthritis (RA). Filgotinib is characterized by predominantly inhibition of JAK1 and its efficacy and safety have been highlighted by phase 2/3 studies, but no real-life data in RA are currently available.ObjectivesThe aim of this study was to evaluate the effectiveness and safety profile of filgotinib in real-life setting in RA patients included in Italian GISEA (Group for the Study of Early Arthritis) registry.MethodsFor this study, data from RA patients treated with filgotinib recorded in Italian GISEA registry were analysed. Disease activity scores and patients reported outcomes (PROs) were compared at baseline and six months follow-up using paired t-tests. The retention rate was estimated by the Kaplan-Meier method, while a cox regression model was used to search for possible factors influencing drug survival.ResultsOne hundred and seventy-nine patients (female 89.4%, age 57.8±12 years, FR/ACPA+ 64.3%, current/former smoker 31.8%) included in GISEA registry started filgotinib for active RA. Most patients were taking filgotinib as second (23.5%) or further (43%) b/tsDMARDs line of treatment. Filgotinib was used in monotherapy in 66.5% of patients, while 52% were not on treatment with glucocorticoids (GCs) at baseline. All demographic and clinical data are reported in Table 1. A follow-up visit was available for 122 patients (mean time of first follow-up visit: 4±2 months). As shown in table 1, we observed a decrease of all disease activity scores and PROs. At first follow-up visit, 67.8% of patients were in remission/low disease activity according to CDAI and 65.4% according to SDAI. Kaplan-Meyer analysis highlighted that drug persistence was similar either in monotherapy or combination therapy (Figure 1a), and irrespective of GCs at baseline (Figure 1b). However, a better persistence was observed in RA patients on first line treatment with filgotinib (Figure 1c). Thirty-five patients stopped filgotinib during follow-up, 10 for lack of efficacy, 4 for loss of efficacy, 4 for adverse events, while for the remaining cases the cause of drug discontinuation was unknown. No major cardiovascular events were reported. Finally, univariate Cox-regression model showed that b/tsDMARD naïve patients had a lower risk of drug discontinuation (naïve vs other lines: HR 0.37, 95%CI 0.20-0.86).ConclusionIn Italian real-life setting, filgotinib confirms a good effectiveness and safety profile.Table 1.Demographic and disease characteristics at baseline and at first follow-up visit (T1) of RA patients treated with Filgotinib.Variablesbaseline (n. 179)T1 (n. 122)Agemean (SD), years57.8 (12.7)58 (12.6)Gendern. (%), femalen. (%), man160 (89.4)19 (10.6)110 (90.2)12 (9.8)BMIn. (%), underweightn. (%), heathy weightn. (%), overweightn. (%), obese4 (3.8)50 (48.1)21 (20.2)29 (27.9)4 (5.3)36 (47.4)15 (19.7)21 (27.6)Smokersn. (%), currently smokern. (%), former smokern. (%), never smoker13 (13.8)17 (18)64 (68.1)8 (13.5)12 (20.3)39 (66.1)IgG RF/ACPA +n. (%)74 (64.3)54 (71.1)VAS painmean (SD)63.1 (29.1)35 (30.7)***VAS PtGAmean (SD)60 (26.7)35 (29)***VAS PhGAmean (SD)44 (25.4)20.9 (23)***TJC28mean (SD)5.4 (5)2.7 (3.8)**SJC28mean (SD)3.3 (3.5)1.3 (2.2)***DAS28-ESRmean (SD)4.6 (1.3)3.3 (1.4)**CDAImean (SD)19.1 (11.3)9.6 (9.5)**SDAImean (SD)20.5 (12)10.3 (10)**HAQ-DImean (SD)1.3 (0.7)0.9 (0.7)***glucocorticoidn. (%)86 (48)47 (38.5)**Prednisone (equivalent), mg/diemean (SD)5.8 (3.7)3.4 (2.6)*csDMARD (in corso)n. (%)60 (33.5)31 (25.4)b/tsDMARD linen. (%), 1^ linen. (%), 2^ linen. (%), 3^ line or others60 (33.5)42 (23.5)77 (43)/Mean time of first follow-up visit: 4±2 months*p<0.05, **p<0.01, ***p<0.001Figure 1.Survival analysis in RA patients treated with Filgotinib.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Nowadays, numerous therapeutic options are available for patients with rheumatoid arthritis (RA), and the number of patients achieving remission has significantly increased. However, some patients have a disease defined by EULAR as “difficult-to-treat”1 (D2T), which today represents a new challenge for rheumatologists.Objectives:The primary objective was to evaluate the characteristics of the D2T-RA population recorded in the Italian GISEA registry undergoing treatment with b/tsDMARDs. The secondary objective was to assess the effectiveness and changes at 6 and 12 months in disease outcomes, stratifying the analysis by different mechanisms of action.Methods:For this study, data from RA patients treated with b/tsDMARDs recorded in the Italian GISEA registry from January 2017 to December 2023 were analyzed. Disease activity scores and patient-reported outcomes (PROs) were recorded at baseline, and at six- and twelve-month follow-up. D2T-RA patients were defined by meeting these three criteria: 1) failure of ≥ 2 b/tsDMARDs (with different mechanisms of action); 2) signs suggestive of active/progressive disease (at least moderate disease activity according to disease activity scores and/or glucocorticoid treatment ≥ 7.5 mg/day prednisone or equivalent); 3) patient VAS (Visual Analogue Scale) pain and/or PtGA (Patient Global Assessment) and/or PhGA (Physician Global Assessment) > 20. The retention rates were estimated using the Kaplan-Meier method and compared with log-rank test, while repeated measures ANOVA (Analysis of Variance) was used to assess changes in disease activity and PROs during follow-up.Results:The GISEA cohort included 5251 treatment lines with b/tsDMARDs. We were able to assess the D2T category for 3439 cases at the start of a new treatment. Overall, 1060 (30.8%) patients met all three criteria for D2T-RA, while 2379 (69.2%) patients were not categorized as D2T. Table 1 reports the demographic and clinical characteristics of D2T-RA patients. Patients with D2T-RA showed higher disease activity and PRO scores at baseline. Notably, JAK inhibitors (JAKis) were used more frequently in D2T-RA patients (48.8%) compared to non-D2T-RA patients (33.3%, p<0.05).Globally, the 5-year survival rate was significantly lower for D2T-RA patients compared to those with non-D2T-RA (47.5% vs 62.5%, p<0.001). No significant differences in persistence were observed among the classes of b/tsDMARDs used in D2T-RA (log-rank test: 6.76, p=0.15), with a 5-year survival rate of 38.7% for abatacept, 41.2% for TNFi, 48.1% for IL6r inhibitors, 62.3% for anti-CD20, and 49.6% for JAK inhibitors. Figure 1 shows changes from baseline in disease activity scores and VAS pain in D2T-RA according to b/tsDMARD class. DAS28-ESR was reduced in all b/tsDMARD classes, except for TNFi. CDAI was reduced in all b/tsDMARD classes without any differences among the classes. VAS pain was reduced in all classes. For VAS pain, we observed a significant difference between abatacept and JAK inhibitors, with JAK inhibitors showing greater reduction in VAS pain (p<0.05). Also filgotinib, the latest JAK inhibitor approved onto the market, exhibited a significant decrease on pain perception at both time points.Figure 1.Conclusion:Our study provides a snapshot of D2T-RA patients within the GISEA registry. All currently used b/tsDMARDs appear to be effective in this patient cohort. The higher efficacy of JAK inhibitors, particularly in managing pain symptoms in these patients, warrants further investigation.REFERENCES:[1] Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35.Acknowledgements:We thank Ing. Massimiliano Dellisanti Fabiano Vilardi for his valuable contribution to database creation and management.Disclosure of Interests:None declared.