Months Of Biologic Therapy Research Articles

Mucus Plug Score predicts clinical and pulmonary function response to biologic therapy in patients with severe Asthma.

Mucus plugging has been identified as an important feature of severe asthma contributing to airway obstruction and disease severity. Recently, improvement of mucus plugging has been found upon treatment with several biologic therapies. We aimed to analyze associations of baseline characteristic with mucus plugging score (MPS) and asked whether MPS at baseline predicts the clinical and functional response to biologic treatment in patients with severe asthma. We retrospectively analyzed biologic-naïve patients with a suitable CT scan available at baseline. We calculated the MPS and analyzed correlations with baseline parameters and improvements of biomarkers, pulmonary function and clinical parameters after 4 months of biologic therapy. We included n=113 patients in the baseline cohort, hereof n=101 patients with sufficient data after 4-months of biologic therapy for the follow-up analysis. CT showed mucus plugging in 77% of patients with a median MPS of 4. Multivariate regression analysis showed correlation of MPS with lower FEV1 (rho= -0.24, p=0.009) and DLCO (rho=-0.26 , p= 0.01), and higher FeNO (rho=0.36 p=0.0003) at baseline. Patients received treatment with anti-IgE (8.8%), anti-IL5 (27.4%), anti-IL5R (37.2%), anti-IL4R (25.7%) and anti-TSLP (0,9%) in clinical routine. Baseline MPS correlated with improvements of FEV1 (beta=0.72; p=0.01) and ACT (beta= 0.24; p= 0.001) in multivariate regression analysis. Our study suggests that higher MPS correlates with worse pulmonary function at baseline, but also predicts a larger clinical and pulmonary function response to biologic therapies in severe asthma.

Clinical Remission Predictors in Non-Colonized Bronchiectasis and Severe Asthma with Type 2-Targeted Biologic Therapy: A Retrospective Real-Life Pilot Study.

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population.

Disease response in rheumatoid arthritis across four biologic therapies associates with improvement in paraoxonase-1 activity and oxylipins

ObjectiveParaoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme, that has been implicated as a biomarker of cardiovascular risk in patients with rheumatoid arthritis (RA). We aimed to investigate how different...

Plasma Sclerostin Levels in Rheumatoid Arthritis Women on TNF-α Inhibitor Therapy.

Rheumatoid arthritis (RA) is associated with significant systemic and local bone loss. The aim of this study was to assess whether or not 15-month tumor necrosis factor α inhibitor (TNFαI) therapy in combination with methotrexate (MTX) affects circulating levels of sclerostin (SOST) in female RA patients. Plasma levels of SOST were measured using immunoassays kits. Baseline SOST levels showed no significant differences between RA patients and control participants. Postmenopausal women with RA tended to have higher sclerostin levels than premenopausal woman with RA. After 15 months of treatment with TNFαI, plasma levels of SOST were decreased. Before starting biological therapy, circulating levels of SOST significantly correlated with the patient's age (p < 0.05) and the marker of inflammation, such as ESR (p < 0.05). Multivariate regression analysis showed that age was the only significant predictor for baseline SOST levels in women with RA (β = 0.008, p = 0.028, R2 model = 0.293). Moreover, a positive correlation between SOST levels and the 28 joint disease activity score value based on the erythrocyte sedimentation rate (DAS28-ESR) was found at baseline (p < 0.05), as well as after 15 months of biological therapy (p < 0.05). Thus, plasma SOST levels may be helpful for monitoring the efficacy of TNFαI treatment in RA patients. According to our results, TNFαI, in combination with MTX, has a beneficial effect on bone turnover with a significant reduction in bone metabolism marker SOST.

P842 Assessment of body composition parameters in patients with inflammatory bowel disease treated with biological therapy

Abstract Background There is growing evidence of the role of biological therapy (BT) in improving body composition parameters (BCP) in inflammatory bowel disease (IBD) patients. Since myopenia and high adiposity affect prognosis and could lead to treatment failure, there is the need for expanding the assessment of BCP in clinical practice beyond traditional measures like body mass index (BMI). Methods A cross-sectional study included 151 IBD patients treated with BT (80 males, 83 Crohn`s disease, 68 ulcerative colitis, mean age 37). Bioelectrical Impedance Analysis (InBody170) was done to estimate: body weight, BMI, skeletal muscle mass (SMM), body fat mass (BFM), percent body fat (PBF), fat free mass (FFM). Dividing SMM, FFM and BFM by height squared, we calculated the skeletal muscle mass index (SMI), fat-free mass index (FFMI) and fat mass index (FMI). Results In relation to BMI, 84 (55.6%) patients had healthy weight, 41 (27.2%) were overweight, 13 (8.6%) were obese and 13 (8.6%) were classified as underweight. Clinical remission was present in 139 (92.6%) patients. The average values of the measured BCP are as follows: body weight 71.7kg (41.4-123.7); body height 174.6±10.9cm; BMI 23.7kg/m2 (15.1-36.9); PBF 24.6% (5-48); SMI 9.7kg/m2 (6.3-13.5); FFMI 17.5kg/m2 (12.0-23.5); FMI 5.7kg/m2 (1.0-17.3). Muscle mass parameters were significantly higher in the group of patients treated with BT longer than 3 months (SMI p=0.01, FFMI p=0.02), while in the group of patients treated longer than 1 year we observed, apart from muscle mass parameters, a significant increase in adiposity parameters (FMI p=0.02, PBF p=0.06). [WU1] Patients who previously had the need for change of BT type had significantly higher values of FMI (p=0.04). Patients with extraintestinal manifestations (EIMs), compared to the group without EIMs, had statistically significantly lower values of body weight (p=0.02), SMI (p=0.01), and FFMI (p= 0.01). There was no statistically significant difference in BCP by IBD subtype, presence of clinical remission, BT type and protocol, previous operations, corticosteroids, mesalazines and azathioprine use. Conclusion The duration of treatment with BT can significantly affect muscle mass and adiposity parameters, leading to improved muscle mass parameters after 3 months of therapy, while an increase in adiposity markers is observed after 12 months of BT. Our findings suggest a potential association between EIMs and muscle mass alterations, as well as a relationship between the need for a change in BT type and higher adiposity parameters.

Six-Month Follow-Up of Periodontal Condition in Rheumatoid Arthritis and Ankylosing Spondylitis Arthritis Patients Undergoing Anti-Tumour Necrosis Factor-α Therapy.

In our present study, we aimed to assess the effects of anti-TNF therapy on periodontal condition in a mixed cohort of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Moreover, we wished to determine whether the baseline dental condition of these patients would affect response to biological therapy. A cohort of 24 arthritis patients was consecutively recruited before starting anti-TNFα therapy. After the dropout of six patients, we evaluated the dental status of 18 subjects at baseline and after 6 months of biological therapy. Clinical responder (R) and non-responder (NR) status was determined after 6 months of anti-TNF treatment. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), PPDmax, clinical attachment loss (CAL), and CALmax were determined. During the 6-month treatment period, six patients (3 RA and 3 AS) terminated the study prematurely as they did not respond to treatment (NR). Therefore, 18 patients were included in the full analysis. There were no major differences in PI, BOP, PPD, PPD max, CAL, and CALmax, among R and NR patients. TNF inhibition resulted in increased GI (0.65 ± 0.34 vs. 0.88 ± 0.30; p < 0.05), as well as decreased PPDmax (4 ± 1.94 vs. 2.72 ± 1.36; p < 0.05) and CALmax (5.22 ± 2.56 vs. 2.72 ± 1.36; p < 0.05) after 6 months. Eight patients had incomplete canal fillings or dead pulps and/or apical periodontitis; six in the R and two in the NR group. In our present study, anti-TNF therapy seemed to worsen the extent of gingival inflammation (GI); however our results also do not support the reduction of mean CPD and CAL as reported by others.

Incidence of ANA Positivity After the Administration of Biologicals

Background: Antinuclear antibodies (ANA) are often used in diagnosing autoimmune rheumatological diseases, but their behavior in response to biological therapies, particularly in Asian patients, is not well-documented. The impact of these therapies on ANA status is crucial for understanding disease management and treatment efficacy. This study aims to evaluate the prevalence and significance of ANA positivity following the administration of biological agents in patients with autoimmune rheumatological diseases. Methods: This pilot study was a prospective cohort study involving 100 patients with autoimmune rheumatological diseases who were initially ANA negative at baseline. Predominantly included patients were axial spondyloarthritis (AxSpA) (n=95) and ANCA vasculitis (n=5). Patients with AxSpA were diagnosed according to the 2009 ASAS criteria, and treated with biological agents (e.g., TNF inhibitors such as adalimumab, etanercept, or IL-17 inhibitors such as secukinumab) and followed at a tertiary care center in India from January 2021 to December 2023. ANA levels were measured before and after 3, 6, 9, or 12 months of biological therapy. Changes in ANA positivity, clinical outcomes, and correlations with disease activity were analyzed. Results: Out of the 100 patients enrolled, 67 (67%) completed the study. All participants were ANA negative at baseline. After biological therapy, ANA positivity developed in 4 patients (5.9%). Despite this increase in Ana positivity, there was no significant correlation between ANA positivity and clinical disease activity, as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the visual analog scale (VAS) for pain, BVAS suggesting effective therapeutic response despite changes in ANA status. Additionally, 30 patients were lost to follow-up, highlighting challenges related to the financial sustainability of biological therapy in the resource limited countries. Conclusion: Biological therapies for AxSpA are associated with an increase in ANA positivity although this change does not appear to impact clinical disease activity. The rise in ANA titres may reflect disease-related changes or treatment effects rather than a direct correlation with therapeutic efficacy. Further longitudinal studies are needed to understand the clinical significance of these findings and to refine the interpretation of ANA results during biological therapy.

Efficacy, Safety, and Continuation of Biological Therapy in Older Patients with Asthma in a Real-World Setting: A Retrospective Observational Study.

Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma. In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated. Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group. Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.

Prevalence of metabolic syndrome and chronic inflammation in psoriasis before and after biologic therapy: a prospective study.

As a chronic inflammatory disease, psoriasis affects not only the skin but also the metabolic profile of the patients. Biologic therapies, including tumor necrosis alpha (TNF-a) inhibitors and interleukin (IL)-12/23 and IL-17 antagonists, have proven effective in the reduction of psoriasis severity; however their impact on the metabolic and chronic inflammatory profiles of the patients remains incompletely elucidated. We performed a longitudinal case-control study on 106 psoriasis patients and an equal number of controls without the disease, as well as a prospective study on the patient group with the end point being 6 months of biologic therapy. Patients received either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. Abdominal circumference, serum fasting glucose, triglycerides (TG), high-density lipoproteins (HDL), erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured for both patients and controls, with an additional measurement for patients after 6 months. At baseline, the number of psoriasis patients suffering from obesity, metabolic syndrome, and chronic inflammation significantly outnumbered controls (p<0.05), with the calculated odds ratio being 1.88, 6.83, and 81.84 for these conditions in psoriasis, respectively. Biologic therapies increased the abdominal circumference of patients in a slight but significant fashion (p<0.05), as well as significantly improved HDL, CRP, ESR levels at 6 months (p<0.05). Moreover, after 6 months, the number of patients meeting the diagnostic criteria for metabolic syndrome and chronic inflammation was significantly lower than at baseline (p<0.001). According to our results, biologic therapies improve the overall metabolic and inflammatory profiles of psoriasis patients, the most significant ameliorations being noticed for serum HDL, CRP, and ESR.

PSSD and biologic therapy: Real-life data in 417 patients with moderate to severe psoriasis.

Psoriasis is a chronic relapsing immune-mediated disease leading to a strong impact on patient's quality of life. The treatment of psoriasis has undergone a revolution with the advent of biologic therapies. Currently, Psoriasis Area and Severity Index [PASI] and Dermatology Life Quality Index [DLQI] scores are in use to assess the overall severity of pathology. A new self- administered questionnaire, the Psoriasis Symptoms and Signs Diary (PSSD), assesses severity of six psoriasis symptoms (itch, skin tightness, burning, stinging, and pain,) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding). To evaluate and compare the efficacy of biologic therapies through PSSD in patients with moderate to severe psoriasis Methods: The PSSD questionnaire was administered to all the patients at the beginning and after 6 months of biologic therapy (anti-TNFalpha, anti- IL17, anti-IL23, anti-IL12/23 and phhosphodiesterase-4 Inhibitors). The study population included 417 adult patients with moderate to severe psoriasis in treatment with biologic drugs. All the drugs contributed to a significant improvement of mean total PSSD at t 24; anti-IL17 and anti-IL23 led to a significantly greater reduction at t 24 mean PSSD when compared to other therapies. The PSSD, is a new validated instrument useful for capturing psoriasis patient's quality of life and evaluating treatments efficacy. In our study this score has been useful to put in evidence significant differences between biologic drugs.

IMPROVEMENT OF MYOCARDIAL FUNCTION AND DYNAMICS THE LEVEL OF BLOOD BIOMARKERS IN PATIENTS WITH RHEUMATOID ARTHRITIS ON ANTIRHEUMATIC THERAPY

TYPE: Late Breaking Abstract TOPIC: Cardiovascular Disease PURPOSE: to study the dynamics of myocardial dysfunction (lower global longitudinal epicardial strain of left ventrical (GLESLV)), pentraxin, galectin-3 and ST2 levels after biological therapy during 12 month follow-up. METHODS: A total of 19 pts with RA (EULAR) were included: 84% of women, age 53[37;65] years, disease duration 19[8;96] months; DAS28 6,0[5.3;6.8], positive for ACCP (89%), RF (78%), without prior administration of biologic therapy (BT) and CVD. All pts underwent blood pressure monitoring, echocardiography and speckle tracking assessment of GLES LV. Methotrexate therapy was started in 68% pts, leflunomide–2%, glucocorticoids–32%. BT was administered in all RA pts (adalimumab and abatacept). After 12 months 21% of RA pts remained highly disease active. ST2, pentraxin and galectin-3 levels was assessed in 19 pts with RA before and after 12 months of BT. RESULTS: After 12 months GLESLV has increased from -15,9[-14,3;-18,5]% to -18,8[-16,0;-21,0]%,(p<0,04); ST2 level decreased from 13,8[11,5;20,1] to 12,5[9,6;14,5]ng/ml, (p<0,003). The incidence rate of lower GLESLV decreased by 41% (from 67% to 26%, p<0.008), There were no significant changes in the pentraxin and galectin-3 levels in RA pts after BT. After 12 months RA pts with preserved high disease activity had higher level of systolic blood pressure (120[100;130] vs 100[92;117]mm Hg,p<0.001), lower LV ejection fraction (58[56;63] vs 68[60;69]%,p<0.05) and GLESLV (-16,8[-15,0;-18,8]% vs -20,1[-18,0;-21,1]%,p<0.05), than in pts whose disease activity decreased. There were negative correlation between ΔGLESLV and ΔESR (r=-0,4;p<0,03), ΔST2 (r=-0,4;p<0,05). CONCLUSIONS: In RA pts decrease disease activity on BT leads to an improvement in GLESLV and pronounced reduction ST2 levels. CLINICAL IMPLICATIONS: That can contribute to reduce the risk of CVD. DISCLOSURE: No significant relationships.

The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma-COPD Overlap Syndrome.

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma–COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months. Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with ≥1 exacerbation and ≥1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of “controlled” patients (with no exacerbations, no need for corticosteroids and ACT ≥ 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Efficacy and Safety of Abatacept, Adalimumab, and Etanercept in Pediatric Patients With Juvenile Idiopathic Arthritis.

The lack of randomized controlled trials comparing biologics for the treatment of juvenile idiopathic arthritis (JIA) has led to wide variation in treatment approaches. The objective of this study is to compare the efficacy and safety of abatacept, adalimumab, and etanercept in JIA patients treated at a tertiary pediatric institution. This was a single-center, retrospective chart review of patients initiated on abatacept, adalimumab, or etanercept from December 1, 2015, to August 31, 2018, at Monroe Carell Jr. Children's Hospital at Vanderbilt (VCH). The primary outcome was the change in the Physician Global Assessment (PGA) score after 4 to 6 months of biologic therapy. Secondary outcomes included change in laboratory markers of JIA disease activity, change in the number of joints with active disease or limitation of motion, reduction in corticosteroid dose, adverse effects, adherence among patients who have their medications filled at the institution's specialty pharmacy, and reason for discontinuation of therapy. A total of 139 patients were included, with a median age of 13 years. Most patients, 80.6%, experienced a reduction in their PGA score after starting biologic therapy. There was not a statistically significant difference among the agents (p = 0.64). Adverse effects were reported in only 26.6% of patients, with the most frequent being injection site reactions or pain (n = 35). Ultimately, 32% of patients discontinued biologic therapy with a lack of efficacy being the most common reason. Abatacept, adalimumab, and etanercept were not significantly different in efficacy and safety for the treatment of JIA at this single institution.

Differences in Biologic Utilization and Surgery Rates in Pediatric and Adult Crohn's Disease: Results From a Large Electronic Medical Record-derived Cohort.

Crohn's disease (CD) is a chronic illness that affects both the pediatric and adult populations with an increasing worldwide prevalence. We aim to identify a large, single-center cohort of patients with CD using natural language processing (NLP) in combination with codified data and extract surgical rates and medication usage from the electronic medical record (EMR). Patients with CD were identified from the entire Cleveland Clinic EMR using ICD codes and CD-specific terms identified by NLP to fit a logistic regression model. Cohorts were developed for pediatric-onset (younger than 18 years) and adult-onset (18 years and older) CD. Surgeries were identified using current procedural terminology (CPT) codes and NLP. Crohn's disease-related medications were extracted using physician orders in the EMR. Patients with pediatric-onset (n = 2060) and adult-onset (n = 4973) CD were identified from 2000 to 2017 with a positive predictive value of 98.5%. Rate of CD-related abdominal surgery over time was significantly higher in adult-onset compared with pediatric-onset CD (10-year surgery rate 49.9% vs 37.7%, respectively; P < 0.001). Treatment with biologics was significantly higher in pediatric vs adult-onset CD cohorts (63.6% vs 49.2%; P < 0.001). The overall rate of CD-related abdominal surgery was significantly higher in those who received <6 months of a biologic compared with ≥6 months of a biologic for both cohorts (pediatric 64.1% vs 39.1%, P ≤ 0.001; adult 69.3% vs 56.5%, P ≤ 0.001). Additionally, 60.9% in pediatric-onset CD and 43.5% in adult-onset CD treated with ≥6 months of biologic therapy have not required abdominal surgery. On multivariable analysis, perianal surgery was a significant risk factor for abdominal surgery in both cohorts. We used a combination of codified and NLP data to establish the largest, North American, single-center EMR cohort of pediatric- and adult-onset CD patients and determined that biologics are associated with lower rates of surgery over time, potentially altering the natural history of the disease.

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases.

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma.

Inhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy. We examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74-0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab. Out of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74-100)% versus 60 (27-100)%; p=0.031) and exacerbations (AER change -2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02-9.94; p=0.045). ICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.

Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients’ clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count–erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

NEWER BIOLOGICAL AGENTS IN THE TREATMENT OF SEVERE ASTHMA: REAL WORLD RESULTS FROM A TERTIARY REFERRAL CENTER

SESSION TITLE: Asthma: From Blood Biomarkers to Biologics and Disease Burden SESSION TYPE: Original Investigations PRESENTED ON: 10/21/2019 1:30 PM - 2:30 PM PURPOSE: Biologic pharmacotherapy in the form of anti-interleukin 5 (IL-5) inhibitors (mepolizumab and reslizumab), IL-5 receptor antagonists (benralizumab), and IL-4 and IL-13 inhibitors (dupilumab) are relatively new therapies for the treatment of severe, refractory asthma. The available literature on the efficacy of these agents is mostly limited to the randomized controlled trials performed for drug approval purposes. We report on the usage as well as efficacy of these agents in a real world clinical setting from a tertiary referral center. METHODS: This retrospective chart review of electronic medical records was performed for all patients with severe asthma who underwent biologic pharmacotherapy at Mayo Clinic in Rochester, Minnesota between January 2016 and December 2018. Extracted data included demographic patient information, baseline asthma characteristics, as well as spirometry results. Only patients receiving biologic therapy for ≥ 6 months very included in the study. RESULTS: Over the study period, we identified 50 patients (29 female) receiving one of the newer biologic agents for ≥ 6 months. Median age at treatment onset was 54 (range 22-88 years). A total of 8 patients were initiated on benralizumab and 42 on mepolizumab with a median follow up duration of 9 months post drug initiation. The median number of years of oral prednisone use prior to biologic initiation was two years. There was a significant decline in the median number of asthma exacerbations in the 12 months before and after drug initiation (4 vs. 1; p= 0.0020). Similarly; there was a significant reduction in the median dose of prednisone in the 6 months before and after drug initiation (20mg vs. 5 mg; p= 0.0010). The FEV1 did not change significantly after both 6 and 12 months of biologic therapy compared to baseline FEV1. CONCLUSIONS: We present a long term, real-world clinical experience of the use of newer biological agents in the management of oral steroid dependent asthmatics. We are able to demonstrate significant effectiveness of these agents in reducing asthma exacerbations as well as oral steroid dosages in this difficult patient population. CLINICAL IMPLICATIONS: This study confirms the long term benefit of extended biologic therapy use in severe, refractory oral steroid dependent asthma. DISCLOSURES: No relevant relationships by Megan Dulohery Scrodin, source=Web Response No relevant relationships by Vivek Iyer, source=Web Response pharmaceutical drug trial site invest. relationship with GSK Please note: $1-$1000 Added 03/17/2019 by Karina Keogh, source=Web Response, value=Travel monograph relationship with BMJ Please note: $1-$1000 Added 03/17/2019 by Karina Keogh, source=Web Response, value=Honoraria No relevant relationships by Kaiser Lim, source=Web Response No relevant relationships by Ashokakumar Patel, source=Web Response No relevant relationships by Dayne Voelker, source=Web Response

Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of Infection.

(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy were independently associated with an increased infection risk. (2) Methods: A prospective longitudinal study of patients with RA treated with tocilizumab was conducted. RA patients treated with an antitumor necrosis factor α monoclonal antibody were also included as a control group. The primary outcome was occurrence of infection during the first 24 months of biologic therapy. (3) Results: A total of 15 patients were included, with a mean age of 51.0 ± 4,1 and 73.3% (n = 11) female. A multivariate survival regression model, adjusted for confounding factors, was fitted for each of the iron metabolism variables. Hazard ratios for being above the median of each parameter was considered. Transferrin saturation above the median value (>32.1%) was associated with a higher infection risk (HR 4.3; 95%CI 1.0–19.69; p = 0.05). Similarly, although non-significantly, higher serum iron was strongly associated with infection occurrence. (4) Conclusions: This study identified a probable association between infection risk and higher serum iron and transferrin saturation in patients with RA on anti-IL-6R biologic therapy. We suggest that both these parameters should be considered relevant contributing factors for infection occurrence in patients on anti-IL-6R therapy.