Efficacy Of Biologic Therapies Research Articles

Efficacy of Biologic Therapies in the Management of Allergic Rhinitis: A Systematic Review

Efficacy of Biologic Therapies in the Management of Allergic Rhinitis: A Systematic Review

Long-Term Outcomes of Patients with Biologically Treated Psoriatic Arthritis and Atopic Dermatitis-A Single-Center Experience.

(1) Background: Although the association between psoriasis and atopic dermatitis (AD) is reported in the literature, scarce data are known about the efficacy of biologic therapy (including TNF and IL-17 inhibitors) in patients with psoriatic arthritis (PsA) and concomitant AD. (2) Objective: We aimed to explore AD in patients with PsA undergoing biologics for their active disease, focusing on prevalence and clinical and potential therapeutic implications. (3) Material and methods: We performed a retrospective analysis of 64 patients with PsA receiving various biological agents, followed-up in an academic outpatient rheumatology department up to 10 years. (4) Results: Atopic diseases were reported in about one third of cases, with a higher incidence of AD (10 cases; 52.6%) vs. atopic rhinitis (6 cases; 31.6%) and allergic asthma (3 cases; 15.8%). Three morphological patterns of AD were recognized including chronic prurigo (3 cases), a chronic lichen simplex (1 case), and eczemas (6 cases). All PsA with concomitant AD displayed a late onset of skin atopy (in their adult life) and demonstrated a specific profile (younger), from urban settings, equally distributed among genders, and requiring switching to a higher number of biologics to achieve disease control. (5) Conclusion: PsA and AD may coexist, requiring special attention when selecting the optimal biologic agent.

Changes in cytokine complexes in children with autoimmune diseases with different effectiveness of their biological therapy

Introduction. Cytokines (CC) play an important pathogenetic role in the development of autoimmune diseases. Over the past decade, there has appeared a huge number of biological drugs that target certain cytokines. The main problem remains the choice of a suitable biological drug, as up to 40% of patients do not respond to treatment or become resistant to it. Aim: to identify informative cytokine complexes in children with psoriasis, MS, and IBD with different efficacy of biological therapy. 
 Materials and methods. Two hundred eighty eight children with autoimmune diseases were examined against the background of supportive biological therapy. Patients were divided into groups of exacerbation and remission depending on the lesion area index PASI for psoriasis (PS), clinical activity indices PUCAI for ulcerative colitis (UC), PCDIA for Crohn’s disease (CD), by the pre­sence of foci of demyelination on MRI for patients with multiple sclerosis (MS). All patients underwent a study of 25 cytokines in serum samples using multiplex analysis (X-MAP technology).
 Results. In PS, MS, UC, and CD patients, an increase in pathogenetically significant cytokine profiles associated with cells (c) and functions (f) of M1 cells, Th1, Th2, Th17 was revealed in the exacerbation of diseases relative to the groups in remission. There was a significant decrease in the levels of cytokines and cytokine complexes in patients with MS relative to patients with PS, UC and CD, with the exception of cTh1. Threshold values of the level of cytokine complexes above which the development of an exacerbation of the disease can be expected were obtained: for PS — 1431.1 pg/ml (fTh22 — IL13 + Il22), for PC — 33.1 pg/ml (cTh1 — IFN-γ + IL12p70 + TNF-β + IL2), UC — 20.9 pg/ml (M1 — IL-1 + IL-6 + TNF-α), CD — 1986 pg/ml (fIL12 — IL12 + IL23 + IL27).
 Conclusion. To assess the effectiveness of biological therapy and to predict the condition of patients, it is possible to evaluate specific cytokine complexes for a specific pathology.

Safety and Efficacy of Biologic Therapies (Ustekinumab and Vedolizumab) in the Treatment of Inflammatory Bowel Disease (IBD): A Systematic Review

Safety and Efficacy of Biologic Therapies (Ustekinumab and Vedolizumab) in the Treatment of Inflammatory Bowel Disease (IBD): A Systematic Review

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register

Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Biologic drugs in the treatment of juvenile dermatomyositis: a literature review.

There is no clear consensus in the literature regarding the choice of biologic therapies and efficacy in juvenile dermatomyositis (JDM). In this review, we aimed to examine previous studies regarding biologic drug use in JDM patients. We screened MEDLINE and Scopus for articles involving JDM patients treated with biologic drugs. We identified 74 articles describing 495 JDM patients treated with biologic drugs (538 biologic treatments) during our literature search. The median (min-max) age of these patients was 9.8 (1-17) years (F/M:1.8). The most frequently used biologic drugs were rituximab (RTX, 50%) and tumor necrosis factor (TNF) inhibitors (34.8%). In a few cases, abatacept (4.3%), anti-interleukin-1 agents (0.9%), tocilizumab (0.9%), bortezomib (0.4%), ustekinumab (0.2%), eculizumab (0.2%), and golimumab (0.2%) were used. RTX was most frequently preferred in patients with severe skin involvement (46.3%). Improvement with RTX was obtained in 60.1% of RTX treatments. Infliximab was most frequently preferred in calcinosis (43.3%), while adalimumab in skin involvement (50%) and etanercept in resistant/recurrent diseases (80%). Improvement was achieved in 44.4% of anti-TNF treatments. Adverse events were observed in 46.8% (58/124) of all treatments. Our results suggest that biologic agents may be a promising alternative for the treatment of particularly resistant JDM cases. Controlled studies are required to provide higher level of evidence for the timing of biologic use in JDM treatment. Key Points • There is no consensus on the choice and efficacy of biologic therapies in JDM. • RTX and TNF inhibitors are the most commonly used biologic drugs. • Biologics were especially preferred in severe skin involvement, calcinosis, and resistant diseases.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Hidradenitis suppurativa should be recognized as a weight-related comorbidity in National Institute for Health and Care guidelines on managing obesity.

We propose hidradenitis suppurativa (HS) is added to the list of weight-related comorbidities in the new National Institute for Health and Care Excellence guideline on obesity. Effective obesity management in patients with HS could help reduce disease severity, pain and cardiovascular risk, and improve quality of life and the efficacy of biologic therapy. In addition, it could reduce the costs of HS-associated care (GP visits, hospital outpatient attendances, biologic drugs, inpatient admissions, elective and emergency surgery).

Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

ObjectiveThere are numerous biological therapies and small molecules licensed for luminal Crohn’s disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this...

Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis

ObjectiveBiological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is...

The Efficacy of Sequential Biologic Agents in Refractory Rheumatoid Arthritis after Failure of Initial DMARD and anti-Tumor Necrosis Factor Therapy

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study.

BackgroundThe efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including body mass index (BMI).ObjectiveThis study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m2).MethodsA multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006–December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables.ResultsFive hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m2 compared with those with a BMI ≥ 30 kg/m2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan–Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI.ConclusionsObesity (BMI ≥ 30 kg/m2) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01080-z.

ImmTORTM to amplify the efficacy and reduce immunogenicity of biologics.

In recent months as vaccines against the SARS-CoV-2 virus continue to rollout across the globe, there has been a renewed interest in ways to activate or ignite the immune system. For a vaccine to be effective, it must be immunogenic and specific to provoke the body's defenses to mount an effective response that protects the host from disease. However, there are other situations wherein the immune system mounts an unwanted immune response that can be detrimental to health, either directly, by causing an autoimmune disease, or indirectly, by compromising the safety and/or efficacy of biologic drugs. In these scenarios, it would be desirable to have a 'tolerogenic vaccine' that could selectively and effectively mitigate these unwanted immune responses. ImmTORTM, a nanoparticle technology, is being developed to address the issue of immunogenicity for gene therapy vectors and other biologic drugs. By targeting antigen-presenting cells, ImmTORTM has the potential to amplify the efficacy of biologic therapies and unlock the full potential of such treatments to improve the lives of those who suffer from serious and debilitating diseases.

Biological Therapies or Apremilast in the Treatment of Psoriasis in Patients with a History of Hematologic Malignancy: Results from a Retrospective Study in 21 Patients.

BackgroundFew studies addressing the safety and efficacy of biological therapy (BT) or apremilast (APR) in patients with psoriasis with a history of hematologic malignancy (HM) exist.AimTo describe the tolerance and efficacy of BT and APR in moderate-to-severe psoriasis in patients with a history of in-remission or evolving HM.MethodologyA retrospective, multicenter chart review of the tolerance and efficacy of BT or APR in patients with moderate-to-severe psoriasis and a clinical history of in-remission or evolving HM.ResultsTwenty-one patients with severe psoriasis and a history of HM were included in France by the GEM Resopso study group. Of the 16 patients treated with one or more BT lines, none showed recurrence of their HM which was considered as stable or in remission, and only 2 patients showed an evolution of their HM which had been considered as stable at the beginning of treatment. In the 10 patients treated with APR, the HM of one patient who also received BT worsened. The 3 evolutions did not impact the treatment with BT or APR. Tolerance was very satisfactory, with a low occurrence of infections. Regarding efficacy, only one patient treated with APR did not achieve any notable clinical improvement.ConclusionDespite supportive data regarding tolerance, the heterogeneity of the analyzed population and limited available data, BT and APR should be used with caution in this patient population and investigations on larger cohorts should be conducted to further assess their tolerance in this patient population.

Safety and Efficacy of Biological Therapy in Chronic Antibiotic Refractory Pouchitis: A Systematic Review With Meta-analysis.

Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis in patients with ulcerative colitis. Those with ≥3 episodes of pouchitis/year and symptoms despite antibiotics are considered to have chronic antibiotic refractory pouchitis (CARP). While several agents including probiotics, steroids and immunomodulators have been used, treatment of CARP remains challenging. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of various biological agents in treatment of CARP. Multiple databases were searched through June 2020 for studies that reported the efficacy and safety of biological therapy including antitumor necrosis factor-alpha agents [infliximab (IFX) and adalimumab (ADA)], vedolizumab (VDZ), and ustekinumab in CARP. We excluded studies on Crohn's like and/or other inflammatory complications of the pouch. Meta-analysis was performed to calculate pooled rates of clinical as well as endoscopic improvement and remission. We included 15 studies with 311 patients in our final analysis. Ninety-two patients were treated with IFX, 42 with ADA, 144 with VDZ and 33 with ustekinumab. Pooled rate of clinical improvement was 71.4%, 58.2%, 47.9% and clinical remission was 65.7%, 31%, 47.4% with IFX, ADA, and VDZ, respectively. Pooled rate of endoscopic improvement was achieved in 61.2% patients treated with VDZ while endoscopic remission was achieved in 70.3% patients treated with IFX. Adverse events were reported in 3.9% patients. Biologic therapy is safe and effective in the treatment of CARP.

Polymorphisms Involved in Response to Biological Agents Used in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic disease that leads to joint destruction. During the last decade, the therapy of RA has been principally based on biological drugs. Although the efficacy of biological therapy has been established, patients demonstrated a high heterogeneity in clinical response to treatment. Several genetic polymorphisms play a part in the different response to biological drugs. This review summarizes the pharmacogenetics of biological agents approved for clinical RA treatment. We reviewed PubMed papers published over the past 20 years (2000–2020), inserting as the search term “rheumatoid arthritis and polymorphisms”. Despite some studies showing important correlations between genetic polymorphisms and response to biological therapy in RA patients, most of these findings are still lacking and inconsistent. The personalized treatment according to a pharmacogenetics approach is promising but the available pharmacogenetics data on biological treatment in RA are not adequate and reliable to recommend pharmacogenetic tests before starting biological therapy in RA patients.

P287 Patient sex does not affect endoscopic outcomes of biologicals in patients with inflammatory bowel disease, but is possibly associated with adverse events: A systematic review

Abstract Background There are several known factors influencing the efficacy and tolerability of biological therapies. Whether patient sex affects this is currently unclear, yet this knowledge would be helpful for risk and benefit stratification. This study assesses the role of patient sex on the efficacy and tolerability of biological therapies used for the treatment of IBD. Methods A systematic literature search was performed on 08 April 2019 using Embase (including Medline), Medline OvidSP, Cochrane Central Register of Controlled Trials, Web of Science and Pubmed. The primary outcome was the influence of patient sex on endoscopic outcomes in IBD patients treated with biologicals. The secondary outcome was the influence of patient sex on adverse events during biological therapy. Studies examining either of the outcomes were included in the assessment, regardless of study type or setting. Results The search yielded 19461 citations. After review 55 studies were included in the study, involving 28465 patients treated with adalimumab, certolizumab pegol, infliximab or vedolizumab. Of the 41 studies that objectively examined patient sex and efficacy of biological therapy, none found a significant association. Of the 14 studies examining patient sex and adverse events, 7 found that adverse events such as infections or skin lesions occur more frequently in female than in male patients. No meta-analysis of the primary or secondary outcome could be performed due to lack of exact reporting of summary measures. Conclusion There is no evidence for a sex difference in endoscopically measured response to biological therapies in IBD patients. However, there is a possible influence of sex on the occurrence of adverse events with a higher incidence in females.

Mo1897 - Safety and Efficacy of Biologic Therapies for Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholangitis: An IBD Remedy Study

Mo1897 - Safety and Efficacy of Biologic Therapies for Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholangitis: An IBD Remedy Study

Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients?

Objective: To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients.Method: This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10–19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status.Results: The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11–20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4–53.8), 38.6 (30.3–46.8), and 50.1 (41.8–58.4); p < 0.001, respectively].Conclusion: In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Biological therapy of traditional therapy-resistant adult-onset Still's disease: an evidence-based review.

BackgroundBiotherapy is becoming increasingly important in the treatment of adult-onset Still’s disease (AOSD). The aim of our study was to evaluate the efficacy and safety of biological therapy for AOSD resistant to traditional therapy.Patients and methodsDatabase of Library of Congress, the PubMed, and Web of Science Core Collection were used to retrieve relevant articles published in English language until March 2017. Only studies published in English language were included, and the additional references quoted in these articles were also checked. Articles concerning the efficacy and safety of all the biotherapies in refractory AOSD were evaluated.ResultsThere were 112 articles available in total; 422 AOSD patients were given at least one biologic. We found that 293 patients (69.43%) had received TNF-α blocking agents (infiliximab, etanercept, and adalimumab), 194 patients (45.97%) were treated with IL-1 receptor antagonists (anakinra, rilonacept, and canakinumab), 163 patients (38.63%) were given IL-6 inhibitor (tocilizumab), and 24 patients (5.69%) received rituximab and abatacept. The efficacy of biological therapy and overall tolerance of biological therapy for refractory AOSD were good. Thirty two of 271 patients given anti-TNF-α therapies (11.81%), 116 patients receiving IL-1 inhibitors (65.54%), 124 patients receiving tocilizumab (76.07%), and 13 patients given other biological therapies (36.11%) achieved remission. Side effects of biologic therapy were infections such as urinary tract infections and soft tissue abscess.ConclusionOur findings suggest that anakinra and tocilizumab may be good choices for the treatment of refractory AOSD considering the effectiveness and safety.