Introduction Of Biological Treatment Research Articles

Treatment Impact on the Long-Term Ocular Outcomes in Behçet’s-Related Uveitis

ABSTRACT Purpose To examine the demographic characteristics, findings and complication rates in patients with Behçet’s uveitis (BU) and to investigate the effect of early biological therapy on the development of complications. Methods Medical records of 94 patients with BU were retrospectively reviewed. Demographic data, ocular findings and complications at presentation, complications during follow-up, and treatments received during follow-up were analyzed. Patients who were followed for at least 24 months were divided into two groups according to the time of presentation as Group 1 (between 2009 and 2015) and Group 2 (between 2016 and 2021). Complications at the time of presentation and during follow-up, and treatments were compared. Results We enrolled 94 patients with a male-to-female ratio of 1.94 with a mean age of 30 ± 12 years. Median follow-up was 58.1(12–163) months. There were 35 patients (66 eyes) in Group 1 and 33 patients (61 eyes) in Group 2. At the time of presentation, end-stage disease, cataract, epiretinal membrane, and optic atrophy were significantly more common in Group 1 than in Group 2 (p < 0.05). A significantly higher proportion of eyes in Group 1 developed macular edema, cataract, epiretinal membrane, and macular atrophy during-follow-up (p < 0.05). Median time to initiation of biological treatment was 17.29 months in Group 1 and 3.33 months in Group 2 (p < 0.001). The overall complication rate was significantly lower in Group 2. Conclusions Prognosis of BU is improved after the introduction of biological treatment. Early use of biological agents in BU is effective in decreasing sight-threatening ocular complications.

Disease Activity Patterns of Paediatric Inflammatory Bowel Disease - A Danish Nationwide Cohort Study (1996-2018).

Inflammatory bowel diseases (IBD) are heterogeneous in the frequency and severity of their flare-ups. We aimed to describe disease activity patterns in a Danish nationwide paediatric IBD cohort. Paediatric patients (<18 years at diagnosis) with Crohn's disease (pCD) or ulcerative colitis (pUC) in the study period from 1996 to 2018 were identified in national registers. Disease activity (severe, moderate-to-mild, remission) was assessed at diagnosis according to medications prescribed, hospitalisations and surgeries. 1,965 pCD and 1,838 pUC incident patients were included in the cohort. At diagnosis, severe disease activity was found in 87%/80% of pCD/pUC in addition to 6.1% of pUC patients had undergone a colectomy during the first year after diagnosis. Five years after diagnosis, the annual proportions of pCD/pUC with no disease activity were 70%/72%, and 10 years after diagnosis the proportions were 61%/64%. Colectomy was required in 6.1%, 12% and 16% of pUC patients after 1, 5 and 10 years.No improvement of disease activity was seen in the proportion of prevalent pCD (N=2,515) and pUC (N=2,428) in the study period 2000-2018 concomitant with the introduction of biological treatment. Albeit decreasing disease activity was the most common pattern in both pCD and pUC (43% and 47%), respectively. pIBD was characterised by a high proportion of patients with severe activity at diagnosis, followed by an improvement after five and ten years of follow-up. Notably, the proportion of patients with no disease activity was unchanged when biological treatment was introduced and the number of colectomies in pUC remained high.

Association of patient-reported disease burden and treatment switching among patients with plaque psoriasis on nonbiologic systemic therapy

Introduction: Better understanding of the relationship between quality of life and treatment patterns in psoriasis may help guide therapeutic algorithms. This study evaluated the association between patient-reported disease burden and treatment switching from nonbiologic to biologic therapy in patients with plaque psoriasis enrolled in the CorEvitas Psoriasis Registry.&#x0D; Methods: This cross-sectional study included biologic-naive patients aged ≥18 years who had used nonbiologic systemic therapy 28–365 days prior to their registry enrollment between April 2015 and August 2022. A switch to biologic therapy was defined as the introduction of biologic treatment up to 45 days post-enrollment, in addition to or in place of the initial nonbiologic systemic therapy. Measures of patient-reported disease burden collected at enrollment were: the Dermatology Life Quality Index (DLQI); Work Productivity and Activity Impairment Index (WPAI); itch, skin pain, fatigue, and Patient Global Assessment (PGA), measured on visual analog scales (VAS); and the EuroQoL 5-Dimension, 3-Level (EQ-5D-3L) questionnaire. The association between each patient-reported disease burden measure and switching to biologic therapy was evaluated using multivariable logistic regression models, adjusting for age, sex, race, ethnicity, work status, body mass index, psoriasis duration, psoriatic arthritis status, disease severity, number of prior nonbiologic therapies used, and history of difficult-to-treat areas. A secondary analysis stratified each model by patients with PASI scores ≤2 or &gt;2.&#x0D; Results: Of 848 patients included in the analysis, 323 (38.1%) switched to biologic treatment at enrollment. Significantly higher odds of switching were observed for patients reporting greater vs lesser burden on the DLQI (adjusted odds ratio [aOR] = 1.55; 95% CI, 1.08–2.23); VAS measures of itch (aOR = 2.14; 95% CI, 1.49–3.08), skin pain (aOR = 2.18; 95% CI, 1.45–3.29), fatigue (aOR = 1.66; 95% CI, 1.15–2.40), or PGA (aOR = 3.09; 95% CI, 1.94–4.91); or WPAI activities impairment (aOR = 2.51; 95% CI, 1.72–3.65). Numerically higher odds of switching were observed for greater vs lesser burden measured by EQ-5D-3L. In the secondary analysis, 52 of 330 patients with PASI scores ≤2 (15.8%) switched to biologic treatment. Among patients with PASI scores ≤2, those with greater vs lesser burden for VAS itch, skin pain, or PGA, or with impairment of their usual activities as measured by EQ-5D-3L had significantly higher odds of switching to biologic treatments.&#x0D; Conclusion: Data collected from real-world patients with plaque psoriasis suggest that, in addition to disease severity, patient-reported disease burden, such as itch and skin pain, may be an important driver of switching from a nonbiologic to biologic therapy, even among patients with a low degree of skin involvement.&#x0D; Sponsored by: CorEvitas.

Monitoring the effect of TNF-alpha inhibitors on laboratory parameters and adverse effects in different diseases: a retrospective, single-center study.

The introduction of biological treatments has revolutionized the management of moderate-to-severe psoriasis. Multiple clinical trials have established the efficacy of biological agents in the treatment of moderate-to-severe psoriasis. Nevertheless, there are no clear indications for optimal monitoring intervals during treatment. Collect and analyze laboratory evaluation data from patients receiving biological therapy to provide a better understanding of the need for laboratory investigations before and during treatment with biological agents, and to analyze adverse events and other factors. Retrospective cohort SETTINGS: Tertiary care center in Riyadh, Saudi Arabia. Data were collected from the electronic medical records of patients attending the dermatology, rheumatology, and gastroenterology clinics from June 2014 to June 2019. The laboratory parameters of patients who have received one of the TNF-alpha inhibitors (adalimumab, etanercept, or infliximab) were collected starting at baseline and up to at least one year from treatment initiation. The time points at which patients developed significantly abnormal laboratory results during treatment with one of the TNF-alpha inhibitors. 250 patients RESULTS: Most patients were treated with adalimumab (38.4%); a similar proportion (38%) with infliximab, whereas only 23.6% were treated with etanercept. The majority of the significant abnormal laboratory results occurred at baseline, 3-6 and 9-12 months. Most abnormalities were among patients using infliximab, followed by etanercept, and then adalimumab. The median number of laboratory abnormalities for dermatology patients was significantly lower than that for gastroenterology patients (P<.001), and for rheumatology patients (P=.002). Because dermatology patients showed a lower median number of laboratory abnormalities than patients treated by other specialties in our study, we believe that dermatology patients require less frequent laboratory monitoring. Therefore, we recommend laboratory evaluation at baseline, after 3-6 months, 1 year from the beginning of treatment, and annually thereafter for patients using TNF-alpha inhibitor agents. However, more frequent testing might be warranted according to patient comorbidities, concomitant medications, and physician judgment. Single center and retrospective design. None.

The potential role of biological treatment of chronic rhinosinusitis with nasal polyps: a nationwide cohort study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a challenge to treat despite appropriate pharmacological therapy and endoscopic sinus surgery. With the introduction of biological treatment, costs will increase. In this study, we determine the number of patients with CRSwNP treated with endoscopic sinus surgery and revision surgery and thereby fulfil the main criterion for treatment with biologics in the newest European guidelines. Furthermore, we estimate a potential number of recipients of biologics nationwide. All adult patients registered in the Danish National Patient Registry as having undergone first endoscopic sinus surgery for CRSwNP from 2012â€"2018 were included. The number of operations, surgery dates, and comorbidities were extracted. The Kaplan-Meier method was used to calculate the revision rate over time. Revision surgery was used as a surrogate to determine the pool of potential recipients of biologics, as these would fulfil the eligibility criteria and ensure the necessary cost-effectiveness. A total of 4667 operated patients with CRSwNP were included out of a population of 4.7 million adults (incidence 14/100,000 person-years). Approximately 18% (120 per year) was estimated to have revision surgery within seven years. The median time to revision surgery was 22 months. Of all analysed patients, 21% had registered asthma and/or allergic rhinitis, while these diseases were registered in 34% of patients treated with revision surgery. In Denmark, an average of 120 operated patients annually will have revision surgery within seven years and may benefit from treatment with biologics as an alternative option to revision surgery.

Platelet indices as potential biomarkers for determining active ulcerative colitis and assessing the efficacy of biological treatment – experience of a single centre – a pilot study

Abstract Various laboratory parameters are commonly used to assess the efficacy of biological treatment (BT). The aim of our study was to assess the correlation between platelet (PLT) indices: (mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW)), C-reactive protein (CRP) and endoscopic picture in the course of infliximab induction regimen in ulcerative colitis (UC) patients. The study enrolled 46 patients with UC – 32 men and 16 women. They were administered infliximab (standard induction therapy). Laboratory tests (CRP and PLT indices) and colonoscopy were performed in all patients during the induction regimen – at 0, 2, and 6 weeks and in follow-up six weeks after the completion of induction therapy. The study revealed a statistically significant decrease in CRP and PLT, and an increase in MPV, together with improvement of endoscopic picture (p &lt;0.001) (MAYO score, MAYO endoscopic subscore) in all patients. PCT and PDW values remained in normal ranges before BT and after the finish of the induction regimen. PCT correlated positively with CRP before the introduction of BT (p = 0.018). In addition, positive correlations between PCT and PLT count were noticed before infliximab induction regimen and in follow-up after the finished of therapy (p &lt;0.001). Additionally, a negative correlation between PLT count and MPV prior to the first dose of infliximab was observed (p=0.032). Our data suggest that PLT indices could be useful biomarkers for determining active UC and for assessing the efficacy of BT. From what we know, this is the first survey devoted to PLT parameters in Polish patients with UC.

Efficacy of biological treatment in inflammatory bowel disease – a single-center experience

Abstract Introduction. Efficacy of biological treatment (BT) is a key issue among inflammatory bowel disease (IBD) patients. Laboratory markers and endoscopic procedures are basic diagnostic tools in the assessment of response to biological agents in the course of Crohn’s disease (CD) and ulcerative colitis (UC). Aim. The aim of our investigation was to assess the correlation between laboratory parameters and endoscopic picture in the course of BT in patients with IBD – CD and UC–treated with biological agents. Material and methods. The total number of 71 patients were enrolled in the study, 25 with CD and 46 with UC. When it comes to 15 patients with CD, they were treated with infliximab (IFX) and 10 patients with adalimumab (ADA) – one year of therapy. Patients with UC were administered IFX – induction therapy. Laboratory tests (C-reactive protein (CRP) and platelet (PLT) count) and colonoscopy were performed in all patients before and during BT. Results. BT improved endoscopic picture (SES-CD, MAYO) in all patients. BT lowered CRP (p&lt;0.05) and PLT count (p&lt;0.05) in CD group. CRP level and PLT count decreased in UC group, too (p&lt;0.05). A positive correlation between PLT count and SESCD score prior to the first dose was noticed in ADA group. CRP level correlated positively with PLT count in CD patients treated with IFX before the introduction of BT. Moreover, CRP level correlated positively with both MAYO score and MAYO endoscopic subscore after the second dose of IFX and after finished induction regimen in UC group. Discussion. BT revolutionized a natural history of IBD and its efficacy was approved worldwide. Nevertheless, biological agents do not lead to a full remission of the disease in all patients. Because of this reason, laboratory parameters and endoscopic picture must be carefully monitored during BT to achieve the best outcome in IBD patients. Conclusion. Full clinical and endoscopic remission of IBD was not achieved, although BT lowered CRP level, PLT count and improved endoscopic picture of patients enrolled into our study.

Biosimilars in paediatric inflammatory bowel disease.

The introduction of biological treatments has changed disease outcomes for patients with inflammatory bowel disease. Biologicals have high efficacy, and can induce and maintain remission after failed responses to conventional immunosuppressive and/or steroid therapy. The increasing occurrence of severe disease at diagnosis has resulted in infliximab being more often introduced as the first-line treatment in a “top-down” approach. Besides their favourable efficacy and safety profile, biologicals have one significant disadvantage, which is their high cost. This results in many patients stopping therapy prematurely, with the maintenance phase being too short. This often leads to disease exacerbation shortly after treatment cessation. Every newly started course of biological therapy can induce production of anti-drug antibodies, which can result in treatment failure and possible allergic/anaphylactic reactions. The introduction of biological biosimilars was intended to greatly reduce therapy costs thus increasing the availability of these agents to more patients. It was also anticipated that biosimilars would prevent premature termination of therapy. Analyses of paediatric data suggest that biosimilar infliximabs are equally effective as the reference infliximab. Safety patterns also seem to be similar. Paediatric experience places cost-therapy reductions at around 10%-30%.

The Price of the Successful Treatment of Pediatric Malignancies.

Recent improvements in therapy of children with cancer have resulted in an increase in cure rates which lead to long-term survivorship. Assessment of short- and long-term complications and late effects of cancer therapies is accomplished by pediatric oncologists and multi-disciplinary team, including continuation of care from pediatric to adult primary care. The late complications of cancer treatment include growth and development, reproduction, vital organ function (cardiac, pulmonary, renal, gastrointestinal), dental, ocular, esthetic sequellae, and second neoplasms (benign or malignant), which are cited as the second most frequent cause of death in the Children Cancer Survivors Study cohort. Long-term follow-up guidelines for survivors of childhood cancers has been established by international specialists, the main aim is to decrease severe late complications by individualizing prevention care and treatment. Preventive measures include reduction of radiotherapy doses, or omission, introduction of new radiotherapy techniques, decrease doses of alkylating drugs, and anthracyclines, cardio protectors, fertility preservations guidelines, new surgical techniques, introduction of biological treatments. The multidisciplinary team monitors certain treatments including risk-based care not only of the tumor, but also premorbid conditions, and health behaviors. More comprehensive and high-quality evaluations of survivorship programs are needed, for long term outcome, quality of life and psychosocial support.

Biosorption of Copper usingOryza sativaandAspergillus oryzae

Heavy metals are ubiquitous and persistent environmental pollutants that are introduced into environment via industrial operations. Copper affect environment as well as humans and animals when in excess concentration. Removal of copper from environment can be performed by physical, chemical and biological methods. Physical and chemical methods are the traditional approaches for treatment of copper in environment. Disadvantages in conventional treatment have led to the introduction of biological treatments for removal of the heavy metals. The search for alternative and innovative treatment techniques has focused on the biosorption activity of biological substances including living cells as well as certain plants. In this study, biosorption of copper by Oryza sativa and Aspergillus oryzae was studied. Biosorption with these biological substrates are cost effective and highly efficient. The experiment deals with a comparison of biosorption of copper in terms of optimum metal concentration, biomass concentration, rate of remediation and effect of pH on the process of biosorption using Oryza sativa and Aspergillus oryzae. Flame Atomic Absorption Spectroscopy (FAAS) was used to quantify metals in the synthetic effluents. Initial and final metal concentrations were estimated to establish the optimum values of the parameters.

The use of biologics for severe psoriasis

Psoriasis is a life-long chronic relapsing dermatosis that shows waxing and waning of disease despite of a lot of conventional treatment. Severe psoriasis, usually defined by a psoriasis area and severity index (PASI) score of more than 10 and an area of involved skin of more than 10%, is a typical indication for biologic therapy. TNF-α inhibitors (etanercept, infliximab, and adalimumab) and an IL-12/23 inhibitor (ustekinumab) are the major biologics currently available for psoriasis. After the introduction of biologic treatment, many patients with severe psoriasis experience dramatic improvement of their disease without many side effects and are able to maintain a long-term remission period. Long-term follow up of the side effects of currently available biologics reveals no increase in adverse events compared with non-psoriatic individuals. However, the high cost of psoriasis biologics is a major remaining hurdle for the prescription of these agents to patients with severe psoriasis.

Anti-TNF therapy for juvenile idiopathic arthritis-related uveitis

Juvenile idiopathic arthritis-related uveitis is the most common type of uveitis in childhood and one of the main causes of visual impairment in children. The introduction of biological treatment has widened the range of therapeutic options for children with uveitis refractory to standard nonbiologic immunosuppressants. Data from clinical trials suggest that both adalimumab and infliximab have demonstrated effectiveness and safety in open-label studies, although no large, randomized, controlled trials have been reported so far. The role of etanercept in treating juvenile idiopathic arthritis-related uveitis is not yet well defined. In our experience, anti-tumor necrosis factor therapy has been shown to be more effective than steroids and/or methotrexate in treating uveitis. Up to now, tumor necrosis factor blocking compounds have been reserved for the treatment of the most severe cases of refractory uveitis, and larger prospective clinical trials are required in order to better assess the safety of these new compounds.

PReS-FINAL-2095: Older age predicts poor response to 6-months methotrexate therapy in a juvenile idiopathic arthritis cohort of patients

The identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of biological treatments.

AB1165 Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: Results from the dutch arthritis and biologicals in children register

BackgroundCurrently, biological agents are not approved for the treatment of persistent oligoarticular juvenile idiopathic arthritis (oJIA). However, there are persistent oJIA patients unresponsive to the conventional treatment consisting of NSAIDs,...

Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch Arthritis and Biologicals in Children Register

Because TNF inhibitors are not approved for persistent oligoarticular JIA (oJIA), although they are used off-label, we evaluated their effectiveness in patients in this category. Persistent oJIA patients were selected from the Dutch Arthritis and Biologicals in Children (ABC) register, an ongoing multicentre prospective study that aims to include all Dutch children with JIA using biologic agents. Response was assessed by the JIA core-set disease activity variables and modified Wallace criteria for inactive disease. Until February 2011, 16 persistent oJIA patients (68.8% females) had been included in the register. Median age of onset was 8.4 years [interquartile range (IQR) 2.1-13.5 years]; history of uveitis in 18.8%; ANA-positive 56.3%. All had previously used MTX, and 81.3% had used IA CSs. Median follow-up after the introduction of biologic treatment was 13.7 months (IQR 8.3-16.7 months). Fourteen patients started etanercept and two patients who had active arthritis as well as uveitis started adalimumab. Although patients with persistent oJIA had few affected joints [median of two active joints at the start of biologic (IQR 1-3)], the patient/parent assessments of pain [median visual analogue score (VAS) 51 (IQR 1-64)] and well-being [median VAS 44 (IQR 6-66)] were high. Additionally, their physician evaluated the disease activity as moderately high [median VAS 36 (IQR 4-65)]. After 3 months this decreased to 0 (IQR 0-30) and 63% achieved inactive disease. After 15 months the disease was inactive in 9/10 observed patients. TNF inhibitors were tolerated well. TNF blocking agents seem an effective and justifiable option in persistent oJIA when treatment with IA CS injections and MTX has failed.

The role of tocilizumab in the management of rheumatoid arthritis

Introduction: The introduction of biological treatments has improved the outlook for patients diagnosed with rheumatoid arthritis. There are now a range of different agents, targeting various pathways involved in the inflammatory process. Tocilizumab, a fully humanised anti-interleukin-6 receptor monoclonal antibody is licensed for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis.Areas covered: This article reviews and appraises the available evidence regarding the efficacy and safety of tocilizumab in rheumatoid arthritis, as identified in PubMed and Embase searches.Expert opinion: Clinical trial data suggest that tocilizumab has similar efficacy both clinically and in reducing structural progression to that seen with the TNF inhibitors. Patients who might be particularly suitable for tocilizumab are those who have failed multiple TNF inhibitors, those with a high inflammatory response as part of their disease and those unable to tolerate methotrexate, given the good responses seen with monotherapy.

Nationwide linkage analysis in Scotland to assess mortality following hospital admission for Crohn’s disease: 1998–2000

Although population-based studies of patients with Crohn's disease (CD) suggest only a modestly increased mortality, recent data have raised concerns regarding the outcome of CD patients requiring hospitalisation. To determine the mortality and contributory factors in 1595 patients hospitalised for CD in Scotland between 1998 and 2000. The Scottish Morbidity Records database and linked datasets were used to assess longitudinal patient outcome, and to explore associations between 3-year mortality and age, sex, comorbidity, admission type and social deprivation. The standardised mortality ratio (SMR) at 3 years from admission was calculated with reference to the Scottish population. The SMR was 3.31 (95% confidence interval 2.80-3.89). This was increased in all patients, other than those <30 years at presentation, and was highest in patients aged 50-64 years (SMR 4.84 [3.44-6.63]). On multivariate analysis, age >50, admission type, comorbidity, social deprivation and length of admission were significantly associated with mortality. Other than age, admission type was the strongest factor predictive of death. Three-year crude mortality was 0.3% for elective surgical, 8.7% for emergency surgical, 8.3% for elective nonsurgical and 12.7% for emergency nonsurgical admission (P < 0.001). The study demonstrates high mortality rates in patients hospitalised during 1998-2000 for CD, especially in patients over 50. Elective surgery is associated with lower mortality than emergency surgery or medical therapy. Further study is needed to determine whether these patterns have changed following the introduction of biological treatment.

A retrospective single-study analysis of survival outcomes in metastatic colorectal cancer.

e14137 Background: Colorectal cancer (CRC) is the third most common cancer in the UK with approximately 20% of patients (pts) presenting with metastatic disease. In 2008 there were over 16,000 deaths from CRC in the UK. The treatment of metastatic colorectal cancer has changed significantly over the last decade. Developments in cytotoxic agents, the use of combination chemotherapy and the introduction of biological treatments have made incremental survival gains. The UK has poorer survival rates from certain cancers when compared to its European counterparts, with a significant poor outcome of patients in the east end of London; This is thought to be due in part to the later diagnosis of cancer.Here a retrospective single centre analysis of survival data is reported in pts treated with palliative chemotherapy for locally advanced and metastatic CRC over a 10 year period. Methods: The survival data in pts with metastatic and locally advanced CRC treated between the years 2000 to 2010 was analysed. Results: 482 pts were deemed suitable for palliative chemotherapy. Pt characteristics of the analysed population was equally distributed over the years analysed. No differences in survival regarding age or gender were uncovered. A significant survival improvement was observed for the pts treated from 2007-2010. Overall survival from 2000-2002 was 11.6months (n=136), 2003-2006 10.9 months (n=174) and 2007-2010 (n=189) 16.0 months. This compares to the overall UK survival (13.7 months) and Europe(20.6 months). Conclusions: This retrospective analysis demonstrates a significant improvement in overall survival over the last 3years of pts with metastatic CRC treated at a UK tertiary referral centre. This is likely to be attributable to a variety of factors including the introduction of biological agents, developments in cytotoxic agents, the use of combination chemotherapy, improvements in supportive care and better patient selection for treatment. Updated data analysis will be made available at the meeting.