Introduction Of Biological Agents Research Articles

Behçet's disease: incidence, prevalence, and real-word data on the use of biologic agents in Japan.

Behçet's disease (BD) is an autoinflammatory disease that can affect multiple organs, including the gastrointestinal tract. Conventional management comprises anti-inflammatory drugs such as glucocorticoids (GCs) and/or immunomodulators that alleviate symptoms. The introduction of biological agents that target tumor necrosis factorα (TNF-α) has improved disease management. The goal of this work was to analyze the current prevalence and incidence of total BD and gastrointestinal Behçet's disease (GIBD) in Japan, and examine treatment trends, especially regarding the use of TNF-α inhibitors (TNFαi). We performed a retrospective descriptive observational study in which BD and GIBD demographic trends, medical treatment patterns, and reported adverse events (AEs) were assessed among patients with data recorded between 2017 and 2021 in the Japan Medical Data Center Claims Database (now JMDC Inc.). Prevalence of BD and GIBD in Japan during the observation period increased at an annual rate of + 3% and + 4%, respectively, while incidence decreased by - 5% and - 2%, with a more prominent decline in confirmed GIBD cases (- 15%). Although GCs were the most common initial treatment administered, use of TNFαi for BD and GIBD management increased by + 5.6% and + 8.1%, respectively. Severe AEs (mainly pneumonia and GI-associated AEs) were reported in 40% of patients receiving TNFαi; however, a high retention rate (of up to 80%) was observed 3years after treatment initiation. The use of TNFαi for GIBD treatment has increased in Japan in recent years. Additional research is necessary to further evaluate TNFαi effectiveness in GIBD and other BD subtypes.

Progress in targeted therapy for ankylosing spondylitis: A review.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial osteoarticular inflammation and tendon enthesitis with unclear pathogenesis. Nonsteroidal anti-inflammatory drugs and antirheumatic drugs used in the traditional treatment of AS have some problems such as drug intolerance and inadequate treatment response. Since the introduction of biological agents in the treatment of AS, they have completely changed the treatment concept of AS, and because of their safety and good tolerance, they have become the main choice for clinical AS patients. This article systematically summarizes the current status of targeted therapy for AS worldwide, analyzes the advantages and disadvantages of different types of biological agents in the treatment of AS, and provides an objective evaluation of clinical targeted therapy for AS, in order to provide a new perspective for clinical standardized treatment.

Effect of genetically engineered drugs in aseptic necrosis of the femoral head in rats

Bone tissue is a dynamic structure with a metabolic function. The maintenance of bone homeostasis is carried out due to the continuous process of its renewal, remodeling. At the same time, a number of pathological processes, such as ischemic catastrophe, can lead to a violation of the balance of maintaining the constancy of the bone structure. One of these diseases is aseptic necrosis of the femoral head. The presented study analyzes the dynamics of expression of genes involved in maintaining bone tissue homeostasis, changes in the histological picture during the development of aseptic necrosis of the femoral head in laboratory rats that did not receive genetically engineered drugs and against the background of the use of inhibitors of biological action IL-6, TNF-α. After induction of aseptic necrosis in the proximal epiphysis of the femur, the histological picture in animals of different groups was not the same. More preserved bone architectonics and a larger volume of bone plates were recorded in rats receiving genetically engineered drugs compared to animals without the introduction of biological agents. The latter also had the most vivid picture of osteodestruction with increased expression of proinflammatory cytokine genes. In animals, against the background of the use of drugs of inhibitors of the biological action of IL-6, TNF-α, from the second week after induction of aseptic necrosis of the mRNA, the profile of the spongiose bone of the proximal epiphysis of the femur tended to increase the expression of osteoreparation genes. At the same time, the greatest inhibition of osteoclastogenesis gene expression was obtained in rats after injection of a monoclonal antibody to the IL-6 receptor.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study

BackgroundEvidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents’ usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. MethodsThis retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. ResultsOf the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). Conclusion: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

Progress of rituximab in the treatment of systemic lupus erythematosus and lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical manifestations, often leading to significant morbidity and mortality, particularly due to lupus nephritis (LN). The standard therapeutic approach involving mycophenolate mofetil, cyclophosphamide, and glucocorticoids has shown limitations due to cumulative toxicity and side effects. The introduction of biologic agents, especially rituximab (RTX), a chimeric monoclonal antibody targeting CD20+ B cells, has revolutionized the treatment landscape. This review synthesized the current understanding of B cells' role in SLE and LN and evaluates RTX's therapeutic impact. B cells contribute to disease pathogenesis through autoantibody production and immune complex formation, leading to tissue damage. RTX's mechanisms of action, including Complement-Dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis, have demonstrated efficacy in both SLE and LN treatment. Clinical studies have reported remission rates and improved renal outcomes with RTX use, although challenges such as human anti-chimeric antibody development and optimal dosing persist. The review emphasized the need for continued research to elucidate RTX's long-term benefits and risks, and to explore personalized treatment strategies that incorporate B cell biology for better disease management in SLE and LN.

Precision Medicine Intervention in Severe Asthma (PRISM) study: molecular phenotyping of patients with severe asthma and response to biologics.

Severe asthma represents an important clinical unmet need despite the introduction of biologic agents. Although advanced omics technologies have aided researchers in identifying clinically relevant molecular pathways, there is a lack of an integrated omics approach in severe asthma particularly in terms of its evolution over time. The collaborative Korea-UK research project Precision Medicine Intervention in Severe Asthma (PRISM) was launched in 2020 with the aim of identifying molecular phenotypes of severe asthma by analysing multi-omics data encompassing genomics, epigenomics, transcriptomics, proteomics, metagenomics and metabolomics. PRISM is a prospective, observational, multicentre study involving patients with severe asthma attending severe asthma clinics in Korea and the UK. Data including patient demographics, inflammatory phenotype, medication, lung function and control status of asthma will be collected along with biological samples (blood, sputum, urine, nasal epithelial cells and exhaled breath condensate) for omics analyses. Follow-up evaluations will be performed at baseline, 1 month, 4-6 months and 10-12 months to assess the stability of phenotype and treatment responses for those patients who have newly begun biologic therapy. Standalone and integrated omics data will be generated from the patient samples at each visit, paired with clinical information. By analysing these data, we will identify the molecular pathways that drive lung function, asthma control status, acute exacerbations and the requirement for daily oral corticosteroids, and that are involved in the therapeutic response to biological therapy. PRISM will establish a large multi-omics dataset of severe asthma to identify potential key pathophysiological pathways of severe asthma.

INFLUENCE OF BACILLUS SUBTILIS ON THE CONDITION AND ACTIVITY OF PHOTOSYNTHETIC SYSTEM OF WINTER WHEAT (TRITICUM AESTIVUM L.) PLANTS

Objective. To assess the performance of individual strains of Bacillus subtilis and the efficiency of their action on the condition and activity of the photosynthetic system of juvenile winter wheat plants (Triticum aestivum L.). Methods. Microbiological, instrumental (microscopic), biophysical (determination of photochemical activity of winter wheat sprouts in model conditions of the induction of chlorophyll fluorescence). Results. The technological stability of B. subtilis H38, H40 and H45 strains was shown both during fermentation (formation of viable spore titre in the range of 1.9‒2.4 billion/mL) and during storage of bacterial suspensions (BS) for 60 days (1.8‒2.3 billion spores/mL). Analysis of the influence of B. subtilis H38, H40, H45 on the activity of the photosynthetic system of winter wheat (Triticum aestivum L.) plants revealed a high informative value of induced changes in chlorophyll fluorescence (ICF), which was recorded in the structural organization of chloroplasts of wheat sprouts at the initial, maximum, and stationary levels of fluorescence and viability index (Rfd after 1:50 dilution of BS of B. subtilis strains is 1.56–1.69; Rfd after 1:100 dilution corresponds to the normal quantum efficiency of photosynthesis in the range of 1.20‒1.40). Conclusion. The studied strains of B. subtilis are characterized by high performance (a significant number of spores are formed during the cultivation of bacteria; their number remains relatively stable during a 60-day research period), which implies the possibility of their successful use in production and the possibility of long-term storage of preparations based on them. The prospective use of the evaluated strains for the intensification of the photochemical activity of winter wheat (Triticum aestivum L.) plants in the process of ontogenesis has been proven. This means scientific and practical importance for ecological monitoring, assessment of plant resistance, and the introduction of biological agents in the technology of growing agricultural crops.

Real-World Safety Profile of Biologics Used in Rheumatology: A Six-Year Observational Pharmacovigilance Study in the Calabria Region.

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. This pharmacovigilance project aimed to study the AEs associated with biologics use in rheumatology. Methods: The current investigation is a multicenter, prospective, observational cohort study based on the Calabria Biologics Pharmacovigilance Program. Patients treated with one biologic agent from January 2016 to January 2022 were enrolled. Results: Overall, 729 (86.3%) of a total of 872 patients did not develop AEs or SAEs, whereas 143 (16.4%) patients experienced at least one AE, of which 16 (1.8%) had at least one SAE. The most common AEs were administration site conditions followed by gastrointestinal, nervous system and skin disorders. We reported a total of 173 switches and 156 swaps. Switches mainly occurred for inefficacy (136; 77.7%), whereas only 39 (22.3%) were due to the onset of an AE. Primary/secondary failure was the most frequent reason for swaps (124, 79%), while AEs onset led to 33 (21%) swaps. Conclusions: This study supports the validity of our program in monitoring and detecting AEs in the rheumatological area, confirming the positive beneficial/risk ratio of biologics.

How has the disease course of pediatric ulcerative colitis changed throughout the biologics era? A comparison with the IBSEN study.

BACKGROUNDIn Korea, infliximab was approved for use in children with ulcerative colitis (UC) in October 2012. AIMTo compare the clinical course of UC before and after the introduction of biological agents, and to compare with the IBSEN study. METHODSPatients under 18 years of age, who were diagnosed with UC and followed from January 2003 to October 2020, were included in the study. Group A (n = 48) was followed for at least 2 years between January 2003 and October 2012, and Group B (n = 62) was followed for at least 2 years between November 2012 and October 2020. We compared endoscopic remission, drug composition, relapse rate, steroid-free period, and the quality of life of each group. We plotted the clinical course of the included patients using the pediatric UC activity index score, and compared our patients with those in the IBSEN study. RESULTSAfter 2 years of treatment, colonoscopy evaluation revealed different outcomes in the two treatment groups. Remission was confirmed in 14 patients (29.2%) of Group A, and in 31 patients (50.0%) of Group B (P < 0.012). The median cumulative corticosteroid-free period was 3.0 years in Group A and 4.4 years in Group B. Steroid-free period of Group B was significantly longer than that of Group A (P < 0.001). There was a statistically significant difference between the two groups in evaluation of the relapse rate during the observation period (P < 0.001). The plotted clinical course graphs of Group A showed similar proportions to the graphs in the IBSEN study. However, in Group B, the proportion of patients corresponding to curve 1 (remission or mild severity after initial high activity) was high at 76% (47/62). CONCLUSIONThe incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent. The clinical course also showed a different pattern from that of IBSEN study. The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC.

Hematologic side effects of biologics and kinase inhibitors used in rheumatologic diseases: a review of the current evidence.

Treatment options for various rheumatologic diseases have been limited until the introduction of biologic agents and kinase inhibitor therapy in recent decades. Since their arrival, they have steadily been integrated into routine management. Given their wide use and overall successful outcomes, it becomes increasingly pertinent for clinicians to readily identify their side effects. Their effects can involve multiple organ systems, including hematologic. This review aims to identify and classify the range of hematologic effects associated with individual biologics and kinase inhibitors used for treatment of rheumatologic diseases.

Postoperative outcomes after degenerative lumbar spine surgery in rheumatoid arthritis patients -a propensity score-matched analysis

BackgroundAlthough treatment options for rheumatoid arthritis (RA) have evolved significantly since the introduction of biologic agents, degenerative lumbar disease in RA patients remains a major challenge. Well-controlled comparisons between RA patients and their non-RA counterparts have not yet been reported. The objective of the present study was to compare postoperative outcomes of lumbar spine surgery between RA and non-RA patients by a retrospective propensity score-matched analysis.MethodsPatients who underwent primary posterior spine surgery for degenerative lumbar disease in our prospective multicenter study group between 2017 and 2020 were enrolled. Demographic data including age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, diabetes mellitus, smoking, steroid usage, number of spinal levels involved, and preoperative patient-reported outcome (PRO) scores (numerical rating scale [NRS] for back pain and leg pain, Short Form-12 physical component summary [PCS], EuroQOL 5-dimension [EQ-5D], and Oswestry Disability Index [ODI]) were used to calculate a propensity score for RA diagnosis. One-to-one matching was performed and 1-year postoperative outcomes were compared between groups.ResultsAmong the 4567 patients included, 90 had RA (2.0%). RA patients in our cohort were more likely to be female, with lower BMI, higher ASA grade and lower current smoking rate than non-RA patients. Preoperative NRS scores for leg pain, PCS, EQ-5D, and ODI were worse in RA patients. Propensity score matching generated 61 pairs of RA and non-RA patients who underwent posterior lumbar surgery. After background adjustment, RA patients reported worse postoperative PCS (28.4 vs. 37.2, p = 0.008) and EQ-5D (0.640 vs. 0.738, p = 0.03), although these differences were not significant between RA and non-RA patients not on steroids.ConclusionsRA patients showed worse postoperative quality of life outcomes after posterior surgery for degenerative lumbar disease, while steroid-independent RA cases showed equivalent outcomes to non-RA patients.

Adalimumab in Pediatric Inflammatory Bowel Disease.

The introduction of biological agents with strong anti-inflammatory action, such as antitumor necrosis factor (TNF) agents, has changed inflammatory bowel disease (IBD) treatment strategy and goals, and has contributed significantly to improve the long-term prognosis of patients. Moreover, several biological agents are being used or researched in pediatric populations. However, only two biological agents, infliximab (IFX) and adalimumab (ADL), are currently approved for children and adolescents. In pediatric IBD, there are limitations and burdens associated with facilitating mucosal healing (MH) when utilizing these two biological agents. ADL is effective in both naïve patients and those with previous experience with biologics. Beyond clinical remission, this drug is also effective for MH and histological remission. The use of therapeutic drug monitoring to further enhance the effectiveness of ADL treatment can be expected to reduce treatment failure of ADL and pave the way for appropriate treatment in the treat-to-target era. This review paper focuses on ADL, examine studies conducted in children, and determine the role this agent plays against pediatric inflammatory bowel disease.

Lower Relapses Rate With Infliximab Versus Adalimumab in Sight-Threatening Uveitis: A Multicenter Study of 330 Patients

PURPOSETo compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA). DESIGNObservational retrospective multicenter study. METHODSA total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti−tumor necrosis factor [TNF]−α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients’ medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety. RESULTSMain etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti−TNF-α agents. CONCLUSIONSIn sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA.

Real-World Data from a Multi-Center Study: Insights to Psoriatic Arthritis Care.

Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2–212; 32% < 4 weeks, 29% 5–12 weeks, 26% 13–28 weeks, 13% with >28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with “good” therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. Conclusions: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.

Real-World Methotrexate Dose on Clinical Effectiveness and Structural Damage of Certolizumab Pegol With Rheumatoid Arthritis.

Objective: Rheumatoid arthritis (RA) treatments have markedly advanced with the introduction of biological agents, e. g., tumor necrosis factor (TNF) inhibitors. TNF inhibitors are demonstrated to be quite effective in combination with methotrexate (MTX), and sufficient doses of both agents are important to control RA's disease activity. However, not all RA patients can be treated with high-dose MTX due to contraindications related to the antimetabolite action of MTX or to tolerability concerns. In daily practice, this has resulted in reduced effectiveness of TNF inhibitors. We sought to determine whether the concomitant use of dose of MTX affected the clinical effectiveness, retention rate, and side effects of certolizumab pegol (CZP) for treating RA in a real-world setting. CZP is a pegylated–conjugated Fab' fragment of a humanized anti-TNF antibody that has high affinity to TNF.Patients and Methods: We divided Japanese RA patients treated with CZP (n = 95, 25–83 years old) into groups based on those with (n = 65) and without (n = 30) concomitant MTX and those treated with a high dose (≥8 mg, n = 41) or low dose (1– <8 mg, n = 24) of MTX. We retrospectively analyzed the concomitant MTX doses' effects and side effects and the patient retention rate.Results: There were no significant differences among the CZP groups with and without MTX or the groups receiving the high vs. low MTX doses in the retention rate, the low disease activity rate, or the inhibitory effect in radiographic joint damage.Conclusion: CZP has the potential to be a useful biological agent to control RA's disease activity and the bone destruction in patients who cannot tolerate a sufficient MTX dose.

Sistemik juvenil idiyopatik artritte son on yılda neler değişti?

Objective: Systemic juvenile idiopathic arthritis (sJIA) is one of seven subtypes of JIA. The aim of this study was to investigate the characteristics, the course and the outcome of sJIA patients in our clinic and to identify what has changed over the last decade in sJIA. Material and Methods: Files of sJIA patients that were followed between March 2002 and April 2019 were evaluated. Results : During the study period 36 patients were diagnosed with sJIA in our clinic (19 were male). Mean age of patients was 81.7±50.1 months at the onset of disease. Most common presenting features were fever (100%), arthritis (83.3%), rash (66.7%) and hepatosplenomegaly (38.9%). Seven patients (19.4%) were diagnosed as macrophage activation syndrome (MAS) due to sJIA. All patients had received corticosteroids. Additional treatments (disease-modifying drugs, intravenous immunoglobulin and biological agents) were given to 29 patients. In our clinic, anti-IL-1 agents have been used since 2011. In this group 26 (72.2%) patients were diagnosed after 2011. After the usage of biological agents, the duration of steroid exposure significantly decreased (p= 0.001). Conclusion: After the introduction of biological agents in the treatment of sJIA, the duration of steroid exposure decreased significantly. Considering anti interleukin (IL)-1 and anti IL-6 treatments among the priority treatments in sJIA patients is important in terms of both providing rapid disease control and reducing side effects related to drugs.

Can serum histone H4 levels predict mucosal healing in Crohn's disease?

IntroductionMucosal healing (MH) has been a treatment target with the introduction of biological agents in Crohn’s disease (CD). Histone H4 increases in chronic inflammation.AimOur goal was to investigate the role of serum histone H4 in predicting MH.Material and methodsThe study included 44 patients who applied to the endoscopy unit for ileocolonoscopic evaluation with the diagnosis of ileocecal CD and 26 healthy controls. After ileocolonoscopic evaluation, we divided the patients into 2 groups: those with and those without MH, according to the presence of endoscopic ulcer or erosion findings. Blood samples were taken from these patients to analyse serum histone H4 before the endoscopic procedure. We first compared serum histone H4 levels between CD patients and the healthy control group and then between those with and those without MH among the CD patients. Finally, we compared CRP, ESR, and serum histone H4 levels in patients with CD according to the presence of MH and symptoms.ResultsSerum histone H4 levels were significantly higher in ileocolonic CD patients compared to the healthy control group (p = 0.002). Also, serum histone H4 levels were significantly higher in CD patients with no MH (p = 0.028) or symptomatic patients (p = 0.033). We did not find a significant difference in C-reactive protein and erythrocyte sedimentation rate levels between CD patients in the presence of MH (p = 0.281 and p = 0.203, respectively) or symptoms (0.779 and 0.652, respectively).ConclusionsSerum histone H4 might be a useful biomarker for MH prediction in ileocolonoscopic CD patients. Validation is needed for large numbers of patients.

AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.

The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Approximately 18.1 × 106 new cases of cancer were recorded globally in 2018, out of which 9.6 million died. It is known that people who have Inflammatory Bowel Disease (IBD) turn to be prone to increased risks of developing colorectal cancer (CRC), which has global incident and mortality rates of 10.2% and 9.2%, respectively. Over the years, conventional treatments of IBD and its associated CRC have been noted to provide scarce desired results and often with severe complications. The introduction of biological agents as a better therapeutic approach has witnessed a great deal of success in both experimental and clinical models. With regard to mesenchymal stem cell (MSC) therapy, the ability of these cells to actively proliferate, undergo plastic differentiation, trigger strong immune regulation, exhibit low immunogenicity, and express abundant trophic factors has ensured their success in regenerative medicine and immune intervention therapies. Notwithstanding, MSC-based therapy is still confronted with some challenges including the likelihood of promoting tumor growth and metastasis, and possible overestimated therapeutic potentials. We review the success story of MSC-based therapy in IBD and its associated CRC as documented in experimental models and clinical trials, examining some of the challenges encountered and possible ways forward to producing an optimum MSC therapeutic imparts.

P660 Evaluating the effectiveness of disease assessment at 2 weeks following a course of oral steroids: Does early intervention affect outcomes?

Abstract Background Early intervention in those patients not responding to a course of oral steroids following an Acute flare of their IBD is essential for improved outcomes. It enables re-assessment and escalation of treatment in those that are non-responders. We present our data on the effectiveness of an IBD nurse-led telephone follow-up appointment two weeks after commencing a course of oral steroids and its impact on outcomes. Methods Data collected prospectively on all patients treated with oral prednisolone between March and November 2019. Partial Mayo score for ulcerative colitis (UC) and clinical assessment of symptoms for Crohn’s disease (CD) patients were used to assess response to treatment at 2 weeks. Results 57 patients were treated with a Prednisolone reducing regime during the 8 months period. Patient demographics included 27 males and 30 females,19 CD and 38 UC patients with a median age of 48 (range 16–88). Following 2 weeks of treatment, 54% (31) of patients reported an improvement in symptoms-19 UC patients (Partial Mayo 0–4) and 12 CD patients. However, 45% (26) patients did not have a clinical improvement at week 2, 19 UC (Partial Mayo 2–9) and 7 CD were still symptomatic. In those patients who had not responded 3 were commenced on Azathioprine, 6 on Methotrexate and one patient had a slow response to steroids. Seven patients were escalated to receive biological therapy (3 vedolizumab, 2 infliximab, 1 ustekinumab and 1 adalimumab). Two other patients had their dose of vedolizumab increased, one patient was switched to another class of biologics. Three patients had a Flexible Sigmoidoscopy and following that 2 were admitted to receive IV steroids and escalated to biological therapy and Methotrexate. One patient was directly admitted for biological therapy, and 2 patients had an alternative diagnosis of Bile Salt Malabsorption which was treated. At the 3 months follow-up period all patients were well and had avoided further admissions or surgery, with only one patient electively opting for surgery. Conclusion Our data show that following a course of oral steroids for a flare of IBD, 45% are still symptomatic after 2 weeks. In this cohort, optimisation of treatment occurred in 23 patients (88%) with either the introduction of biological agents, or early introduction of immunomodulatory therapy. We believe that These data supports the implementation of an early review with appropriate intervention, demonstrating improved patient outcomes.