Immune-mediated Inflammatory Diseases Research Articles

Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies

ObjectivePatients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies...

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Intermittent fasting alleviates IMQ-induced psoriasis-like dermatitis via reduced γδT17 and monocytes in mice.

Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.

P38 Experimental evidence of ecto-5′-nucleotidase (CD73) modulation in psoriasis-like inflammation

Abstract Introduction and aims Adenosine is an endogenous purine nucleoside that, by binding to adenosine receptors, modulates inflammation and immune responses. Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and abnormal differentiation. A2A and A2B adenosine receptors modulate keratinocyte proliferation and their expression was found to be altered in psoriatic epidermis. Ecto-5′-nucleotidase (CD73) is an enzyme that hydrolyses extracellular adenosine monophosphate and represents a key control point for extracellular adenosine accumulation. CD73 is involved in the regulation of local immune response and tissue barrier function. As changes in CD73 expression and activity have been associated with other autoimmune diseases, the aim of this study was to investigate CD73 involvement in skin inflammation using in vitro and in vivo approaches. Methods In vitro experiments were performed on human keratinocyte (HaCaT) cell lines stimulated with tumour necrosis factor-α, interleukin (IL)-17A, IL-6 and IL-1α (10 ng mL−1 each), and in vivo, on the mouse model of imiquimod-induced psoriasis-like inflammation on the right ear, which was also performed on CD73−/− mice and their wildtype counterpart. CD73 expression in cell lysates and ear homogenates were evaluated using Western blot analysis. Results We found that CD73 expression was significantly increased (N = 3 wells, P < 0.05) in cytokine-treated HaCaTs compared with unstimulated cells. In vivo experiments showed increased CD73 expression on psoriatic lesions (P < 0.001, N = 3). In CD73−/− mice, imiquimod-induced lesions were exacerbated compared with the development of lesions in wildtype mice as shown by ear thickness (0.190 ± 0.02 mm, knockout mice vs. 0.138 ± 0.02 mm, wildtype mice; P < 0.05, N = 5), erythema and scaling. Conclusions Our preliminary Results show involvement of CD73 in the development of psoriasis-like inflammation, suggesting that CD73 may represent a new therapeutic target in the treatment of skin diseases. Further investigations are needed to provide an in-depth study of CD73 localization in inflamed skin.

Gene association analysis to determine the causal relationship between immune-mediated inflammatory diseases and frozen shoulder.

Multiple studies have indicated a potential correlation between immune-mediated inflammatory diseases (IMIDs) and Frozen shoulder (FS). To explore the genetic causal relationship between IMIDs and FS using 2-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) summary data for FS were obtained from Green's study, while data for 10 IMIDs were sourced from the FinnGen Consortium. The MR analysis was performed using inverse variance weighting, MR Egger, and weighted median methods. IVW, as the primary MR analysis technique, was complemented with other sensitivity analyses to validate the robustness of the results. Additionally, reverse MR analysis was further conducted to investigate the presence of reverse causal relationships. In the forward MR analysis, genetically determined 4 IMIDs are causally associated with FS: rheumatoid arthritis (odds ratio [OR] (95% confidence interval [95% CI]) = 1.05 [1.02-1.09], P < .01); type 1 diabetes (OR [95% CI] = 1.06 [1.03-1.09], P < .01); hypothyroidism (OR [95% CI] = 1.07 [1.01-1.14], P = .02); and Celiac disease (OR [95% CI] = 1.02 [1.01-1.04], P = .01). However, no causal relationship was found between 6 IMIDs (autoimmune hyperthyroidism, Crohn disease, ulcerative colitis, psoriasis, sicca syndrome and systemic lupus erythematosus) and FS. Sensitivity analyses did not detect any heterogeneity or horizontal pleiotropy. In the reverse MR analysis, no causal relationship was observed between FS and IMIDs. In conclusion, this MR study suggests a potential causal relationship between rheumatoid arthritis, type 1 diabetes, hypothyroidism, and Celiac disease in the onset and development of FS. Nevertheless, more basic and clinical research will be needed in the future to support our findings.

Selective CAR-T cell mediated B cell depletion suppresses interferon signature in SLE.

Applying advanced molecular profiling together with highly specific targeted therapies offers the possibility to better dissect the mechanisms underlying immune mediated inflammatory diseases such as systemic lupus erythematosus (SLE) in humans. Here we apply a combination of single cell RNA sequencing and T/B cell repertoire analysis to perform an in-depth characterization of molecular changes in the immune-signature upon CD19 CAR T cell-mediated depletion of B cells in SLE patients. The resulting datasets do not only confirm a selective CAR T cell-mediated reset of the B cell response, but simultaneously reveal consequent changes in the transcriptional signature of monocyte and T cell subsets that respond with a profound reduction in type 1 interferon signaling. Our current data thus provide evidence for a causal relationship between the B cell response and the increased interferon signature observed in SLE and additionally demonstrate the usefulness of combining targeted therapies and novel analytic approaches to decipher molecular mechanisms of immune-mediated inflammatory diseases in humans.

Biosimilars and access to biologic therapy in immune-mediated diseases

ABSTRACT Background The rise of biologic agents has been a major breakthrough in treating immune-mediated inflammatory diseases (IMIDs). However, their high cost underscores the need for strategies to optimize treatment efficiency. Biosimilars offer cost-effective alternatives to biologics. This study aimed to assess biosimilar drug availability’s impact on biologic therapy access for IMIDs. Research design and methods A retrospective observational study in 15 Spanish hospitals analyzed IMID patients (arthropathies, inflammatory bowel disease and psoriasis) initiating biologic therapy with originator or biosimilar drugs (infliximab, etanercept, adalimumab). Time to availability and initiation of biologic therapy were assessed. Results 267 patients were included, with 58.4% starting on biosimilars. The mean time to availability of the biologic drugs in the hospitals was 15.9 ± 6.7 months, (20.0 ± 12.4 for originator and 11.8 ± 5.2 for biosimilars). Mean time to biologic treatment was 7.7 ± 9.0 years (8.6 ± 8.9 for originators and 7.0 ± 9.0 for biosimilars). Showing statistically significant differences among conditions. Conclusion The emergence of biosimilar drugs has enhanced market competition and accelerated their adoption into hospitals’ therapeutic regimens over original reference drugs. This has significantly improved access to biologic therapy for patients with IMIDs, evidenced by a notable 1.6-year reduction in access time for biosimilar drugs.

Special Issue Entitled “Immune Regulatory Properties of Natural Products”

Although the immunomodulatory effects of natural products have not yet been completely elucidated, attempts to use natural products in the treatment of immune-mediated inflammatory diseases such as autoimmune diseases, chronic inflammatory diseases, mutant viral infections, and even immunosenescence-related cancers are ongoing [...]

Clinical and humoral responses after SARS-CoV-2 breakthrough infections in patients with immunosuppressants

BackgroundDespite impaired humoral responses in patients treated with immunosuppressants (ISPs), recent studies found similar severity of SARS-CoV-2 breakthrough infections compared to controls. One potential explanation is the rapid generation humoral responses upon infection, but evidence is lacking. ObjectivesTo investigate longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infections in patients with immune-mediated inflammatory diseases (IMID) on ISPs and controls. MethodsAs prospective sub-study of the national Target-to-B! (T2B!) consortium, we included IMID patients on ISPs and controls who reported SARS-CoV-2 breakthrough infections between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, three antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at four time points after SARS-CoV-2 breakthrough infections. ResultsWe included 302 IMID patients on ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infections in both groups. However, in IMID patients on anti-CD20 therapy and sphingosine-1 phosphate receptor (S1P) modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild and hospitalization was required in less than 1% of the cases. ConclusionsMost ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones towards new viral variants. However, in patients treated with anti-CD20 therapy or S1P modulators, the dynamics were greatly impaired, and to a lesser extent in those anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

Combined ROS Sensitive Folate Receptor Targeted Micellar Formulations of Curcumin Effective Against Rheumatoid Arthritis in Rat Model.

Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.

Evaluation of the efficacy and safety of cold laser (Diode 808 nm) therapy in the treatment of localized plaque psoriasis: clinical, dermoscopic and ultrastructural study

Background Psoriasis is a chronic, recurring, and immune-mediated inflammatory skin disease. Throughout the period of the last few decades, phototherapy has become widely used in treating stable psoriatic lesions. For the treatment of psoriasis, several light/laser therapies with distinct modes of action have been developed. Cold laser therapy might be an effective therapeutic choice for localized plaque psoriasis. Objective To assess the safety and efficacy of cold laser therapy clinically and microscopically in localized plaque psoriasis treatment. Patients and methods 40 patients with localized mild plaque psoriasis were selected from the Dermatology and Venereology outpatient clinic–Tanta University Hospitals and enrolled in the clinical trial. They were treated by cold laser 808 nm wavelength (Endolaser 422, Enraf–nonious B.V. Rotterdam, Netherlands) one session for 10 min on each plaque twice weekly separated by 2 days until clinical cure or for a maximum of 8 weeks. Evaluation was done immediately after the last session by taking the average of three blinded dermatologists of the photos, the modified Psoriasis Area and Severity Index [mPASI], dermoscopic examination, patients’ satisfaction scale and histopathological and electron microscopic examination of punch biopsy specimens taken before and after the end of treatment from psoriatic lesions in four patients only. Results There was a statistically significant clinical improvement after the end of treatment compared with before treatment as 16 patients (40%) showed excellent improvement, 8 patients (20%) showed good improvement, 9 patients (22.5%) showed mild improvement, and 7 patients (17.5%) showed poor improvement. As regard mPASI, a statistically significant decrease in mPASI was found after the end of treatment (P&lt;0.001). Regarding dermoscopic examination, a statistically significant reduction in the percentage of patients showing dermoscopic red dots and white scales after the end of treatment (P&lt;0.01). As regard the patients’ satisfaction scale, 82.5% of patients were satisfied from the results. Histopathological and ultrastructural evaluation revealed normalization of the psoriatic microscopic changes with cold laser. Conclusion The use of cold laser therapy for the management of localized mild plaque psoriasis is safe, tolerable, effective, and can be used as an alternative therapy for psoriasis.

Effectiveness of secukinumab in patients with psoriasis and psoriatic arthritis in a Saudi real-world setting.

Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient's quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period. This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks. The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%. In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.

Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database

BackgroundAutoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are all immune-mediated chronic inflammatory liver diseases. Autoimmune liver diseases are rare, making identification and treatment difficult. To improve clinical outcomes and enhance patient quality of life, we performed an epidemiological study of autoimmune liver diseases based on real-world comprehensive data.ResultsWe used National Health Insurance Service claims data in Korea from 2005 to 2019. Patients were identified using the International Classification of Disease 10th Revision code, and rare intractable disease codes assigned according to the strict diagnostic criteria. In the AIH cohort, 8,572 (83.9%) were females and the mean age at diagnosis was 56.3 ± 14.3 years. PBC also showed female dominance (83.3%) and the mean age was 57.8 ± 12.6 years. Patients with PSC showed no sex predominance and had a mean age of 57.8 ± 21.5 years. During the study period, there were 10,212, 6,784, and 888 AIH, PBC, and PSC patients, respectively. The prevalence of AIH, PBC, and PSC in 2019 were 18.4, 11.8, and 1.5 per 100,000 population, while the corresponding incidences were 2.3, 1.4, and 0.3 per 100,000 population, respectively. Analysis of sex-age-standardized data showed that the annual prevalence of these diseases is increasing. The 10-year survival rates were 89.8%, 74.9%, and 73.4% for AIH, PBC, and PSC, respectively.ConclusionsThe number of patients with autoimmune liver disease in South Korea is increasing over time. Further research on autoimmune liver disease is needed to fulfill unmet clinical needs.

Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system

In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on the patient population studied. We aimed to analyse severe COVID-19 outcomes and to investigate the effects of the pandemic time period and the risks associated with individual IMIDs, classes of immunomodulatory medications (IMMs), chronic comorbidities, and COVID-19 vaccination status. In this retrospective cohort study, clinical data were derived from the electronic health records of an integrated health-care system serving patients in 51 hospitals and 1085 clinics across seven US states (Providence St Joseph Health). Data were observed for patients (no age restriction) with one or more IMID and for unmatched controls without IMIDs. COVID-19 was identified with a positive nucleic acid amplification test result for SARS-CoV-2. Two timeframes were analysed: March 1, 2020-Dec 25, 2021 (pre-omicron period), and Dec 26, 2021-Aug 30, 2022 (omicron-predominant period). Primary outcomes were hospitalisation, mechanical ventilation, and mortality in patients with COVID-19. Factors, including IMID diagnoses, comorbidities, long-term use of IMMs, and COVID-19 vaccination status, were analysed with multivariable logistic regression (LR) and extreme gradient boosting (XGB). Of 2 167 656 patients tested for SARS-CoV-2, 290 855 (13·4%) had confirmed COVID-19: 15 397 (5·3%) patients with IMIDs and 275 458 (94·7%) without IMIDs. In the pre-omicron period, 169 993 (11·2%) of 1 517 295 people who were tested for COVID-19 tested positive, of whom 23 330 (13·7%) were hospitalised, 1072 (0·6%) received mechanical ventilation, and 5294 (3·1%) died. Compared with controls, patients with IMIDs and COVID-19 had higher rates of hospitalisation (1176 [14·6%] vs 22 154 [13·7%]; p=0·024) and mortality (314 [3·9%] vs 4980 [3·1%]; p<0·0001). In the omicron-predominant period, 120 862 (18·6%) of 650 361 patients tested positive for COVID-19, of whom 14 504 (12·0%) were hospitalised, 567 (0·5%) received mechanical ventilation, and 2001 (1·7%) died. Compared with controls, patients with IMIDs and COVID-19 (7327 [17·3%] of 42 249) had higher rates of hospitalisation (13 422 [11·8%] vs 1082 [14·8%]; p<0·0001) and mortality (1814 [1·6%] vs 187 [2·6%]; p<0·0001). Age was a risk factor for worse outcomes (adjusted odds ratio [OR] from 2·1 [95% CI 2·0-2·1]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001), whereas COVID-19 vaccination (from 0·082 [0·080-0·085]; p<0·0001 to 0·52 [0·50-0·53]; p<0·0001) and booster vaccination (from 2·1 [2·0-2·2]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001) status were associated with better outcomes. Seven chronic comorbidities were significant risk factors during both time periods for all three outcomes: atrial fibrillation, coronary artery disease, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, and cancer. Two IMIDs, asthma (adjusted OR from 0·33 [0·32-0·34]; p<0·0001 to 0·49 [0·48-0·51]; p<0·0001) and psoriasis (from 0·52 [0·48-0·56] to 0·80 [0·74-0·87]; p<0·0001), were associated with a reduced risk of severe outcomes. IMID diagnoses did not appear to be significant risk factors themselves, but results were limited by small sample size, and vasculitis had high feature importance in LR. IMMs did not appear to be significant, but less frequently used IMMs were limited by sample size. XGB outperformed LR, with the area under the receiver operating characteristic curve for models across different time periods and outcomes ranging from 0·77 to 0·92. Our results suggest that age, chronic comorbidities, and not being fully vaccinated might be greater risk factors for severe COVID-19 outcomes in patients with IMIDs than the use of IMMs or the IMIDs themselves. Overall, there is a need to take age and comorbidities into consideration when developing COVID-19 guidelines for patients with IMIDs. Further research is needed for specific IMIDs (including IMID severity at the time of SARS-CoV-2 infection) and IMMs (considering dosage and timing before a patient's first COVID-19 infection). Pfizer, Novartis, Janssen, and the National Institutes of Health.

P021 Uptake, safety, and effectiveness of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide study using data from the Clinical Practice Research Datalink

Abstract Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31st August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n = 2,771) or without (n = 22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..

P017 Planned infliximab use during pregnancy for pakistani patients with immune-mediated inflammatory disease - case series of 12 patients

Abstract Background/Aims Immune-mediated inflammatory diseases (IMIDs) affect mostly young females during their reproductive age. Therefore, a better understanding is needed about the possible disease effects in pregnancy, as well as the risks of fetal exposure to the medications used. Studies have shown that anti-TNF are considered safe and do not increase the risk of adverse events during pregnancy. Nevertheless, the data is quite limited, hence fall in FDA pregnancy category B. We wish to report a series of 12 pregnant women with IMIDs who were intentionally being treated with infliximab for the treatment of active intractable IMIDs. Methods The study included pregnant patients with IMIDs who were treated using anti-TNF between January 2021 to July 2023 at Fatima Memorial Hospital and Doctors Hospital &amp; Medical Centre, Lahore. All patients receiving infliximab were reviewed by a dedicated medical team, who maintained a detailed medical record of each visit. The patients were prospectively followed up and the neonatal outcome was also recorded. Results 12 pregnant women with IMIDs received Infliximab during this study. All these patients required &amp;gt;7.5mg of deltacortil to control their arthritis and hence decision was made to add bDMARDs. 10 patients successfully completed their pregnancies uneventfully and two additional patients are in the later stages of pregnancy. Seven patients had complete remission of their underlying IMIDs and the rest had overall good improvement but continued to have low grade active disease. All our patients presented a satisfactory response to treatment and the pregnancy progressed without any complications. Median gestational week of birth was 38 with a median birth weight of 3490 grams. Conclusion This is the first reported series from Pakistan of intentional infliximab use throughout pregnancy. Our data, combined with many other studies, suggests that anti-TNF is safe during pregnancy and its benefits in achieving control of IMIDs may outweigh the risk of foetal exposure to the drug. This is further supported by the available data suggesting the inflammatory activity as the main risk factor for unfavourable outcome. However, the benefits and risks must be discussed with the patient and management decisions should be taken on individual basis. Disclosure Z. Tayyab: None. M. Haroon: None.

Reactive Oxygen Species-Responsive Dual Anti-Inflammatory and Antioxidative Nanoparticles for Anterior Uveitis.

Anterior uveitis (AU) is an immune-mediated inflammatory disease that results in iritis, cyclitis, glaucoma, cataracts, and even a loss of vision. The frequent and long-term administration of corticosteroid drugs is limited in the clinic owing to the side effects and patient noncompliance with the drugs. Therefore, specifically delivering drugs to inflammatory anterior segment tissues and reducing the topical application dosage of the drug are still a challenge. Here, we developed dual dexamethasone (Dex) and curcumin (Cur)-loaded reactive oxygen species (ROS)-responsive nanoparticles (CPDC NPs) to treat anterior uveitis. The CPDC NPs demonstrated both anti-inflammatory and antioxidative effects, owing to their therapeutic characteristics of dexamethasone and curcumin, respectively. The CPDC NPs could effectively release dexamethasone and curcumin in the oxidizing physiological environment of the inflammation tissue. The CPDC NPs can effectively internalize by activated macrophage cells, subsequently suppressing the proinflammatory factor expression. Moreover, the CPDC NPs can inhibit ROS and inflammation via nuclear transcription factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway activation. In an endotoxin-induced uveitis rabbit model, the CPDC NPs show a therapeutic effect that is better than that of either free drugs or commercial eye drops. Importantly, the CPDC NPs with a lower dexamethasone dosage could reduce the side effects significantly. Taken together, we believe that the dual-drug-loaded ROS-responsive NPs could effectively target and inhibit inflammation and have the potential for anterior uveitis treatment in clinical practice.

P126 Use of oral contraceptives in females with rheumatoid arthritis is not associated with an increased risk of venous thromboembolism: United Kingdom-population based study

Abstract Background/Aims While the use of oral contraceptives in females with immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) is acknowledged as a risk factor for venous thromboembolism (VTE), the interaction between oral contraceptive use and RA is poorly understood. In a large population-based study, we aimed to estimate RA-attributable VTE risk in females using oestrogen contraceptives and/or on hormone replacement therapy (HRT). Methods Females registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) database. Female RA patients and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) were determined using previously-validated algorithms. Female unaffected controls (UCs) were matched 4:1 with RA patients by current age (per year), calendar time, and years since practice registration using nearest neighbour matching, with replacement. Absolute VTE rates over 20 years were compared in RA patients versus matched UCs, overall and in two different subgroups defined by the use of oestrogen contraceptives or HRT. Relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (BMI [body-mass index], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results A total of 82,082 female adults were included in this study, of whom 16,634 were RA patients and 65,448 were UCs. Average study follow-up was 8.3 years (standard deviation [SD]=6.2 years). Female RA patients (mean age 58.3, SD 16.5; mean BMI 27.0, SD 5.9) were similar to matched UCs in their clinical characteristics. Compared to UCs, females with RA were less likely to receive oral contraceptives (RA n = 545 [3.3%], UCs n = 2,542 [3.9], p &amp;lt; 0.001) but more likely to receive HRT (RA n = 752 [4.5%], UCs n = 2,460 [3.8], p &amp;lt; 0.001). Unadjusted VTE events rates were consistently higher in females with RA compared to UCs (430.2 per 100,000 person-years [py], 95% confidence interval [CI]: 396.1, 466.3; UC: 260.5 per 100,000 py, 95%CI: 247.1, 274.4) and in those receiving and not receiving oral contraceptives and HRT. Overall, relative risk of VTE was 52% higher in females with RA compared UCs (adjusted hazard ratio [aHR]= 1.52, 95%CI: 1.36, 1.71, p &amp;lt; 0.001). Compared to UCs, relative risk increases were not statistically significant for females with RA receiving oral contraceptives (aHR 1.43; 95%CI 0.60, 3.63, p = 0.46) and HRT (aHR 2.32; 95%CI 0.92, 5.85, p = 0.08). Conclusion UK data suggest that all women with RA are at a similarly increased risk of VTE irrespective of the use of oestrogen contraceptives or HRT, although larger studies are needed to confirm this finding. It is therefore advisable to conduct routine VTE risk factor assessments for all females with RA. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. A. Barkaway: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; .H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan’s National Health Insurance Research Database

BackgroundTo determine the effect of colchicine on cancer risk in patients with the immune-mediated inflammatory diseases (IMIDs)-related to colchicine use.MethodsThis is a time-dependent propensity-matched general population study based on the National Health Insurance Research Database (NHIRD) of Taiwan. We identified the IMIDs patients (n = 111,644) newly diagnosed between 2000 and 2012 based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)—274,712, 135, 136.1, 279.49, 518.3, 287.0, 696.0, 696.1, 696.8, 420, 429.4, 710.0, 710.1, 710.3, 710.4, 714.0, 720, 55.0, 55.1, 55.9, 556. Inclusion criteria: aged ≧ 20 years, if a patient had at least these disease diagnosis requirements within 1 year of follow-up, and, these patients had at least two outpatient visits or an inpatient visit. After propensity-matched according to age, sex, comorbidities, medications and index date, the IMIDs patients enter into colchicine users (N = 16,026) and colchicine nonusers (N = 16,026). Furthermore, time-dependent Cox models were used to analyze cancer risk in propensity-matched colchicine users compared with the nonusers. The cumulative cancer incidence was analyzed using Cox proportional regression analysis. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (95% CIs) for cancer after adjusting for sex, age, comorbidities, and use of medicine including acetylcysteine, medication for smoking cessation such as nicotine replacement medicines (the nicotine patch) and pill medicines (varenicline), anti-inflammatory drugs and immunosuppressant drugs.ResultsComparing the colchicine nonusers, all cancer risk were mildly attenuated, the (aHR (95% CI)) of all cancer is (0.84 (0.55, 0.99)). Meanwhile, the colchicine users were associated with the lower incidence of the colorectal cancer, the (aHRs (95% CI)) is (0.22 (0.19, 0.89)). Those aged < 65 years and male/female having the colchicine users were associated with lower risk the colorectal cancer also. Moreover, the colchicine > 20 days use with the lower aHR for colorectal cancer.ConclusionColchicine was associated with the lower aHR of the all cancer and colorectal cancer formation in patients with the IMIDs.

Toward Telemonitoring in Immune-Mediated Inflammatory Diseases: Protocol for a Mixed Attention Model Study.

Rheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient's quality of life. Often, delays in outpatient consultations or the patient's difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. The main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. This is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. Participant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. This paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs. ClinicalTrials.gov NCT06273306; https://clinicaltrials.gov/ct2/show/NCT06273306. PRR1-10.2196/55829.