Biologics Research Articles

Similarities and differences between systemic juvenile idiopathic arthritis and adult-onset Still’s disease: a multicenter Spanish study

AbstractTo describe the characteristics of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), compare their presentation and evolution, and analyse possible complication predictors. Multicenter study. Data were retrieved from a hospital-based study of patients with a diagnosis or suspected diagnosis of sJIA or AOSD according to the responsible physician and followed-up for at least one year. Descriptive variables (classification criteria, clinical manifestations, complications, family, and personal history) were collected at disease onset and during follow-up. We present the clinical characteristics of 326 patients, 67% of whom had a diagnosis of sJIA and 33% of AOSD. Clinical manifestation frequencies were similar between the two groups, except for odynophagia, which was significantly more frequent in AOSD than in sJIA (78.4% vs. 25.5%; p < 0.0001). Among the complications, macrophage activation syndrome (MAS) was significantly more common in sJIA than in AOSD (24.4% vs. 9.5%; p = 0.002), to the extent that an sJIA diagnosis significantly increased the risk of MAS, together with serositis presence, and the need for biological therapy. Patients with sJIA and AOSD showed similar characteristics, supporting the idea that they are both part of Still’s disease, but are expressed at different ages. Differences in manifestations and complications might be due to different management between diseases and immune response maturity.

Preferences for Tapering Biologic Disease-Modifying Antirheumatic Drugs Among People With Rheumatoid Arthritis: A Discrete Choice Experiment.

Little is known about the preferences of people with rheumatoid arthritis (RA) regarding tapering of biologic disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to assess the preferences of people with RA in relation to potential treatment-related benefits and risks of bDMARD tapering and the health care service-related attributes that affect tapering. Participants with RA who had experience taking a bDMARD completed an online discrete choice experiment. Participants were asked their preferences when given three hypothetical treatment scenarios in which varying the frequency of treatment might alter their chance of adverse effects, of regaining disease control, and of other health care service-related effects. Preference weights were estimated using a multinomial logit model. There were 142 complete responses. Reduced dosing frequency of bDMARD treatment had the largest impact on preference (mean 1.0, 95% confidence interval [CI] 0.8-1.2), followed by chance of disease flare (mean 0.7, 95% CI 0.6-0.9). Participants were willing to accept an increased risk of flare between 10.6% (95% CI 3.2-17.9) and 60.6% (95% CI 48.1-72.9) in exchange for benefits associated with tapering bDMARDs. Participants with better quality of life were more likely to choose to remain on current treatment. The predicted uptake of bDMARD tapering was high among people with RA, suggesting bDMARD tapering was a favored option. For individuals with RA, making decisions about tapering bDMARDs involves considering several factors, with the most important determinants identified as dosing frequency and the risk of disease flare. Understanding patient perspectives of bDMARD tapering may enable physicians to make patient-focused shared health care decisions.

Reproducible 3D culture of multicellular tumor spheroids in supramolecular hydrogel from cancer stem cells sorted by sedimentation field-flow fractionation

Three-dimensional (3D) cancer models, such as multicellular tumor spheroids (MCTS), are biological supports used for research in oncology, drug development and nanotoxicity assays. However, due to various analytical and biological challenges, the main recurring problem faced when developing this type of 3D model is the lack of reproducibility. When using a 3D support to assess the effect of biologics, small molecules or nanoparticles, it is essential that the support remains constant over time and multiples productions. This constancy ensures that any effect observed following molecule exposure can be attributed to the molecule itself and not to the heterogeneous properties of the 3D support. In this study, we address these analytical challenges by evaluating for the first time the 3D culture of a sub-population of cancer stem cells (CSCs) from a glioblastoma cancer cell line (U87-MG), produced by a SdFFF (sedimentation field-flow fractionation) cell sorting, in a supramolecular hydrogel composed of single, well-defined molecule (bis-amide bola amphiphile 0.25% w/v) with a stiffness of 0.4 kPa. CSCs were chosen for their ability of self-renewal and multipotency that allow them to generate fully-grown tumors from a small number of cells.The results demonstrate that CSCs cultured in the hydrogel formed spheroids with a mean diameter of 336.67 ± 38.70 µm by Day 35, indicating reproducible growth kinetics. This uniformity is in contrast with spheroids derived from unsorted cells, which displayed a more heterogeneous growth pattern, with a mean diameter of 203.20 ± 102.93 µm by Day 35. Statistical analysis using an unpaired t-test with unequal variances confirmed that this difference in spheroid size is significant, with a p-value of 0.0417 (p < 0.05).These findings demonstrate that CSC-derived spheroids, when cultured in a well-defined hydrogel, exhibit highly reproducible growth patterns compared to spheroids derived from unsorted cells, making them a more reliable 3D model for biological research and drug testing applications.

A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease.

The inflammatory bowel diseases (IBD) known as Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.

Immunogenicity of Pneumococcal Polysaccharide Vaccine in patients with rheumatoid arthritis

The presented review searched for articles in the databases PubMed, Web of Science, Scopus, Google Scholar, eLibrary (2002-2022) and assessed the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in adult patients with rheumatoid arthritis (RA), receiving various antirheumatic drugs. The results of this review indicated sufficient immunogenicity of PPV23 in RA patients receiving monotherapy with various biological drugs (bDMARDs) (TNFα inhibitors, IL6 receptor inhibitors, T-lymphocyte costimulation blockers), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and glucocorticoids (GC) in medium and low doses. Monotherapy with methotrexate (MTX), rituximab and combination therapy with bDMARDs +MTX, tsDMARDs+MTX in RA patients reduced the postvaccination pneumococcal response. IgG AT generated in response to PPV23 injection shown functional activity even in RA patients whose antibodies were either lowered in patients receiving MTX or were not detectable at protective values following bDMARD therapy. The potential for pneumococcus antibody production in RA patients receiving therapy with disease-modifying antirheumatic drugs (DMARDs), tsDMARDs and bDMARDs, was concluded. Vaccination against pneumococcal infection should be advised prior to starting therapy due to the likelihood of low antibody levels developing during rituximab treatment.

Terapias biológicas no tratamento de doenças autoimunes: Uma revisão narrativa da literatura

Objective: To analyze biological therapies in the treatment of autoimmune diseases. Autoimmune diseases (ADs) are dysfunctions that occur when the individual's immune system does not have the ability to differentiate what is proper from what is not proper to the body. Among the most prevalent and studied autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Each of these diseases has unique characteristics, although they share the common foundation of a dysregulated immune response (Wang; Wang; Gershwin, 2015; Fallahi et al., 2016). Final thoughts: It is noteworthy that ongoing research and development of new biologic therapies should be prioritized, aiming to further enhance the treatment and management of these debilitating conditions. The medical and scientific community must remain vigilant about the safety and efficacy of these therapies, promoting robust evidence-based clinical practice.

Current and emerging biologic therapies targeting eosinophilic granulomatosis with polyangiitis

Current and emerging biologic therapies targeting eosinophilic granulomatosis with polyangiitis

Harms with placebo in trials of biological therapies and small molecules as induction therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials are the gold standard to assess novel drugs in ulcerative colitis and Crohn's disease. However, there might be risks associated with receiving placebo. We aimed to examine the harms associated with receiving placebo in trials of licensed biologics and small molecules for the induction of remission in ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched MEDLINE, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials from database inception to May 30, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for induction of remission in adults (≥18 years) with moderately to severely active ulcerative colitis or luminal Crohn's disease reporting data on adverse events over a minimum treatment period of 4 weeks. There were no prespecified study exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, any drug-related adverse event, infection, worsening of inflammatory bowel disease (IBD) activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events (VTEs), reporting relative risks (RRs) with 95% CIs. The protocol for this meta-analysis was registered with PROSPERO (CRD42024527341). The search identified 10 826 citations, of which 47 trials including 20 987 patients (14 267 [68·0%] receiving active drug and 6720 [32·0%] receiving placebo) were eligible. The risk of any treatment-emergent adverse event was no different with active drug than with placebo (7660/14 267 [53·7%] patients on active drug vs 3758/6720 [55·9%] on placebo; RR 0·97, 95% CI 0·94-1·00; I2 =36%). However, the risks of worsening of IBD activity (563/13 473 [4·2%] vs 530/6252 [8·5%]; 0·48, 0·40-0·59; I2 =54%), withdrawal due to adverse event (401/13 363 [3·0%] vs 299/6267 [4·8%]; 0·62, 0·48-0·79; I2 =46%), serious adverse event (682/14 267 [4·8%] vs 483/6720 [7·2%]; 0·69, 0·59-0·80; I2 =30%), serious infection (140/14 194 [1·0%] vs 91/6647 [1·4%]; 0·67, 0·50-0·89; I2 =0%), serious worsening of IBD activity (187/11 271 [1·7%] vs 189/5056 [3·7%]; 0·45, 0·34-0·60; I2 =27%), or VTEs (13/7542 [0·2%] vs 12/2981 [0·4%]; 0·45, 0·21-0·94; I2 =0%) were all significantly lower with active drug than placebo. Numbers needed to treat with active drug to avoid these potentially serious adverse events ranged from 23 for worsening of IBD activity to 452 for VTEs. 27 randomised controlled trials were judged as low risk of bias across all domains. Patients with moderately to severely active IBD receiving placebo are more likely to experience significant worsening of IBD activity and some serious adverse events, which might relate to a reduction in risk of these events with active drug. Patients should be counselled about these potential harms, and alternative trial designs to mitigate these harms should be considered. None.

Modern view of surgical treatment of the lesion ileocecal zone in Crohn’s disease: when and how to operate

Crohn’s disease is an inflammatory bowel disease with a chronic recurrent course and a high risk of complications. Crohn’s disease prevalence has been increasing. Despite the era of biological therapy and new therapeutic approaches in the treatment of Crohn’s disease, the role of surgical treatment remains high. This study aimed to analyze the current trends and approaches of surgical treatment localized lesions of ileocecal zone in children with Crohn’s disease. The scientific databases eLibrary, GoogleScholar, MEDLINE, and Embase were searched. The search time interval was 2017–2024. In several recent articles, a trend toward early ileocecal resection in patients with Crohn’s disease was noted. According to some studies in adults, this approach is an alternative option for medical treatment. The advantages of early surgical approach includes decreased surgical complication level, improving the quality of life and reducing the cost of treatment. The timing of early surgical intervention varies. Notably, Crohn’s disease in children has more aggressive character, and early surgical intervention may not only create a therapeutic window of opportunity to control Crohn’s disease but also contribute to improving the long-term results of Crohn’s disease treatment. The role of surgical technique is being studied (the need to include a mesentery with fat wrapping into a resection area or not), the effect of the type of anastomosis on relapse of Crohn’s disease. Analysis of the safety of Kono-S anastomosis and its impact on development recurrence has shown a number of advantages over traditional anastomosis. However, its application in the practice of pediatric surgeons remains isolated. Similar studies are required in children to determine the optimal strategy for the treatment of Crohn’s disease in ileocecal region (determining the role of surgical treatment and type of anastomosis in achieving long-term and deep remission), preventing recurrence of Crohn’s disease and repeated intestinal resections.

Harms with placebo in trials of biological therapies and small molecules as maintenance therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624). Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains. In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD. None.

Clinical Features, Genetic Landscape and Management of Behçet's Syndrome: A Comprehensive Review

Behçet's syndrome is a systemic inflammatory disorder of unknown origin, presenting with diverse symptoms such as recurrent oral and genital ulcers, skin lesions, and uveitis, and can impact multiple organ systems. Diagnosis relies primarily on clinical evaluation due to the lack of specific diagnostic tests. Management requires a multidisciplinary approach to control inflammation and alleviate symptoms, utilizing treatments like corticosteroids, immunosuppressive agents, and biological therapies. The higher prevalence of Behçet's syndrome along the Silk Road points to significant environmental and genetic influences. Despite progress in understanding its clinical manifestations and treatment options, the underlying mechanisms of the disease remain unclear. Future research is crucial to uncover the disease's pathophysiology and refine treatment strategies, aiming to prevent severe complications such as blindness and neurological impairment. This comprehensive review explores the clinical features, genetic background, and management strategies for Behçet's syndrome, highlighting the potential of precision medicine to improve patient care.

Nanomedicines with Versatile GSH-Responsive Linkers for Cancer Theranostics.

Glutathione (GSH)-responsive nanomedicines have generated significant interest in biochemistry, oncology, and material sciences due to their diverse applications, including chemical and biological sensors, diagnostics, and drug delivery systems. The effectiveness of these smart GSH-responsive nanomedicines depends critically on the choice of GSH-responsive linkers. Despite their crucial role, comprehensive reviews of GSH-responsive linkers are scarce, revealing a gap in the current literature. This review addresses this gap by systematically summarizing various GSH-responsive linkers and exploring their potential applications in cancer treatment. We provide an overview of the mechanisms of action of these linkers and their bioapplications, evaluating their advantages and limitations. The insights presented aim to guide the development of advanced GSH-responsive agents for cancer diagnosis and therapy.

Treatment efficacy and patient satisfaction of ustekinumab compared with tumor necrosis factor-alpha inhibitors in Chinese patients with moderate-to-severe psoriasis: a real-world study

Background Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis. Objective This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients. Methods Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group). Results Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p < 0.050). Conclusion Chinese moderate-to-severe psoriasis patients treated with ustekinumab have a better treatment response at 6 months with improved quality of life and patient satisfaction after 3–6 months of treatment when compared to TNFi.

Osteoarthritis in athletes – surgical and non-surgical aspects of treatment

Introduction: Osteoarthritis (OA) is a degenerative chronic process that primarily affects the elderly, but there are also reports of OA in the young and sports-active population. Symptoms of OA usually include pain, joint stiffness, and crepitation. Physical, radiologic, and laboratory tests are required for diagnosis. The main goal of OA treatment is to restore normal function to the joint affected by OA. Methods: A literature search on PubMed was used to collect facts about the relationship between sports and OA and possible treatment methods. All forms of articles were considered in the literature search. Articles that were not written in English were not included. Literature from the library of the Faculty of Medicine in Mostar was an additional source of information. Results: OA occurs more frequently in people who play or have played professional sports. On the other hand, daily exercise has a positive effect on cartilage metabolism. Most articles reported the occurrence of OA in former professional athletes. The joint most commonly affected by OA was the knee. Injuries were a predictive factor for the occurrence of OA, and most studies talk about anterior cruciate ligament injuries. Running and football were the most commonly studied sports. Treatment options include conservative treatment, surgical methods, and biological therapy. Conclusion: Frequent strain and injury in athletes can cause cartilage damage and potentially lead to the development of OA. The benefits of exercise far outweigh the risks of developing OA. In addition, some studies report a significant stimulating effect of exercise on cartilage cell metabolism. Treatment of OA consists of the use of analgesics, intra-articular therapy, and physiotherapy. Surgical methods are considered when conservative approaches are unsuccessful. Biological therapy and similar treatments are the new potential treatments.

Opioid Use and Outcomes in Patients Hospitalized With Acute Severe Ulcerative Colitis.

Opioid use has not been shown to improve hospitalized inflammatory bowel disease patient pain scores and may prolong the length of stay (LOS). Additional clinical implications of opioid use, particularly high amounts, in the hospital setting have not yet been explored. We sought to determine how high opioid use impacts clinical outcomes in acute severe ulcerative colitis (ASUC). In this single-center study, we identified all patients hospitalized with ASUC who received intravenous corticosteroids from July 1, 2014 to December 31, 2021. Clinical outcomes including opioid exposure, cumulative intravenous corticosteroid dose, biologic rescue therapy initiation date, colectomy rate, opioid prescription at discharge, LOS, and hospitalization cost were collected. High opioid use was defined as ≥40 oral morphine equivalents (OMEs) per day. A univariable logistic regression was performed to evaluate the association of high opioid use with ASUC outcomes. 185 eligible hospitalizations for ASUC were evaluated. 75 patients (41%) received opioids during hospitalization, and 20 patients (11%) received ≥40 OMEs/day. High opioid use was associated with a median 3-day delay in biologic rescue therapy initiation when compared with low/no opioid use (P = .02). 70% of patients with high opioid use received an opioid prescription at discharge compared with 10% of those with low/no use (P < .001). Opioid use was not associated with LOS, duration of corticosteroid therapy, colectomy rate, or hospitalization cost. Among ASUC hospitalizations, high opioid use was associated with delayed biologic rescue therapy initiation and higher rates of opioid prescriptions at discharge.

Comparative effectiveness of combined biologic agents versus standard therapies in the treatment of plaque psoriasis: a retrospective analysis.

Plaque psoriasis is a persistent skin disorder that necessitates efficient management. This study investigates the therapeutic effectiveness and timeline for skin lesion resolution in plaque psoriasis patients treated with combined biologic agents compared to standard therapies. Conducted retrospectively between March 2020 and March 2023, the study included 162 patients with moderate to severe plaque psoriasis. Participants were divided into two groups: the Control Group, which received standard treatments, and the Combined Biologic Agent Group, which received additional biologic therapy with secukinumab. Participants in the Control Group received standard treatments, while those in the Combined Biologic Agent Group received standard treatments plus secukinumab. The results showed that the Combined Biologic Agent Group experienced a significantly faster onset of therapeutic effects, with an average time of 3.04 ± 2.25 days compared to 6.12 ± 2.06 days in the Control Group. Additionally, skin lesion resolution occurred more rapidly in the biologic agent group (7.04 ± 2.13 days) than in the control group (14.56 ± 4.73 days). By week 24, the Psoriasis Area and Severity Index (PASI) scores demonstrated a more substantial reduction in the biologic agent group, decreasing from 26.98 ± 11.28 to 2.48 ± 3.01, whereas the control group showed a reduction from 25.82 ± 10.47 to 10.40 ± 7.63. The overall effectiveness rate was higher in the biologic agent group, with no cases of ineffectiveness, compared to a 20.99% ineffectiveness rate in the control group. Furthermore, there was no recurrence of the disease in the biologic agent group, while the control group experienced an 11.11% recurrence rate. Both groups had a similar incidence of adverse reactions, indicating that the addition of biologic agents does not significantly increase the risk of adverse events. These findings suggest that combined biologic agent therapy offers a more effective and faster treatment option for plaque psoriasis without compromising safety. However, larger-scale clinical trials are necessary to validate these results and establish the long-term benefits and safety of this treatment approach in diverse patient populations.

Drug-induced lung disease: a narrative review.

Drug-induced lung disease (DILD) encompasses a broad, highly heterogeneous group of conditions that may occur as a result of exposure to numerous agents, such as antineoplastic drugs, conventional or biological disease-modifying antirheumatic drugs, antiarrhythmics, and antibiotics. Between 3% and 5% of prevalent cases of interstitial lung diseases are reported as DILDs. The pathogenesis of lung injury in DILD is variable, multifactorial, and often unknown. Acute presentation is the most common, can occur from days to months after the start of treatment, and ranges from asymptomatic to acute respiratory failure. The CT patterns are varied and include ground-glass opacities, organizing pneumonia, and diffuse alveolar damage. Notably, there are no clinical manifestations or CT patterns specific to DILD, which makes the diagnosis quite challenging and necessitates a high index of suspicion, as well as the exclusion of alternative causes such as infection, cardiac-related pulmonary edema, exacerbation of a preexisting ILD, and neoplastic lung involvement. Discontinuation of the offending medication constitutes the cornerstone of treatment, and corticosteroid treatment is usually necessary after the onset of clinical manifestations. The prognosis varies widely, with high mortality rates in severe cases. A history of medications related to pulmonary toxicity in patients with new-onset respiratory symptoms should prompt consideration of DILD as a potential underlying cause.

A Meta-Analysis Examining the Effect of Perioperative Biologic Disease-Modifying Anti-Rheumatic Medications on Postoperative Wound Complications in Various Orthopedic Surgeries.

This meta-analysis was designed to compare the risk of postoperative wound complications in various orthopedic surgeries (OSs) affected by the perioperative use of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The odds ratio (OR) and mean difference (MD), with 95% confidence intervals (CIs), were calculated using dichotomous or continuous random or fixed-effect models, based on the meta-analysis data. This study incorporated 14 investigations conducted between 2005 and 2023, encompassing a total population of 19,021 individuals undergoing diverse OSs. Participants who continued their bDMARDs exhibited a substantially higher incidence of postoperative surgical site infections (OR, 1.39; 95% CI, 1.12-1.72, p = 0.002) compared to those who withheld bDMARDs. However, the study did not find any statistically significant difference between the continuation or withholding of bDMARDs regarding delayed wound healing (OR, 2.02; 95% CI, 1.00-4.06, p = 0.05) or disease flares (OR, 0.59; 95% CI, 0.28-1.25, p = 0.17). The results show that patients who continued their bDMARDs had a notably higher incidence of postoperative surgical site infections. However, no significant differences were observed in delayed wound healing or disease flares when compared to those who withheld bDMARDs. It is important to acknowledge the limitations of this analysis, such as the relatively small number of participants and the limited number of studies available for certain comparisons, which may impact the validity of the findings.

Long-term Safety Monitoring and Efficacy Status of Infliximab and its Biosimilars in Psoriasis Management

Abstract: Infliximab (INF), a murine human monoclonal antibody, is a substantially more successful biologic than topical drugs for treating mild to severe psoriasis because it clears the skin rapidly due to its fast onset of action. Loss of responsiveness over time and some adverse effects, especially the experience of infusion reactions, are the major causes of non-compliance with INF medication. Therefore, evaluation of the long-term reliability of anti-tumor necrosis factor (TNF) medications is necessary for the assessment of the risks associated with long-term anti-TNF therapy. For psoriasis, there are registered safety statistics; however, these individuals might not receive the same level of care as those in a randomized study. Few assessments of the safety of anti- TNF medications across indications, including their biosimilars, are present, but it’s still unknown how anti-infliximab antibodies arise and produce harmful effects. INF biosimilars, when subjected to human studies to reduce cost and improve access, provide therapeutic benefits with associated adverse events, showing variations in incidence depending upon varying patient populations and no new safety indications. During therapy, certain individuals develop antibodies against INF, which are believed to be linked to a loss of response (LOR). Additional research aimed at identifying individuals who are susceptible to treatment resistance is likely to assist doctors in accurately selecting the appropriate candidates for anti-TNF-α therapy and enhancing the long-term effectiveness of the treatment. From clinical studies, we expect to learn about how to utilize INF or its biosimilars more effectively in the management of psoriasis. Therefore, the paper focuses on the efficacy and safety monitoring of INF and developed biological therapies.

Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature.

Chronic inflammatory pain is associated with increased expression of interleukin (IL)-1, an inflammatory cytokine, and activity on its receptor (IL-1R). In response, the body produces IL-1R antagonist (IL-1Ra) to reduce this signaling. Autologous conditioned serum (ACS) is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms. This systematic review investigates the effectiveness of ACS in treating pain and disability caused by spinal pathologies. To evaluate the use of ACS as a conservative management option for spinal pathology. A systematic review of PubMed/Medline was performed to identify studies investigating administration of ACS for treatment of any spinal pathology. Six articles were included, comprising 684 patients treated with epidural (n = 133) or transforaminal (n = 551) ACS injections. Patients had an average age of 54.0 years with slight female predominance (53.2%). The lumbar spine was most commonly treated, with 567 patients (82.9%) receiving injections for lumbar radiculopathy (n = 67), degenerative disc disease (DDD) (n = 372), or spinal stenosis (n = 128); cervical injections were performed in 109 patients (15.9%). Mean (SD) follow-up was 21.7 (4.8) weeks from first ACS injection. All studies investigating mechanical lumbar and lumbar or cervical radicular pain reported significant pain reduction at final follow-up compared to baseline. ACS achieved comparable or superior results to lumbar epidural steroid injections. Adverse events were reported in 21 patients (3.1%), with no serious adverse events. ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies, including cervical and lumbar radiculopathies.