Use Of Biological Drugs Research Articles

Drug Survival and Clinical Course of Patients with Cancer Treated with Biologic Therapy for Psoriasis.

Background/Objectives: Patients with treated solid tumors (TST) are a highly heterogeneous and difficult-to-treat population due to the risk of disease progression/recurrence or infection. Methods: We conducted an observational, retrospective, single-center study at the Dermatology Clinic of Turin with a focus on the special population of cancer patients with psoriasis treated with biologics. Results: As of July 2023, 52 psoriatic patients with a prior/concomitant history of malignancy had taken biologic drugs. The median age was 67 years, and the median age of cancer onset was 55 years. The most common tumors were gastrointestinal cancer and melanoma. After the tumor diagnosis, 61% received an anti-IL17 drug; 37 patients continued the initiated biologic therapy, while 12 switched drugs due to secondary inefficacy. The estimated biologic DS was 55.6% at 50 months. Evidence suggests that IL-17 is a key pathogenic factor involved in tumorigenesis, resulting in a lower risk of malignancies in subjects managed with IL-17 inhibitors. Similarly, IL-23 plays a role in suppressing innate immunity and promoting tumor and metastases development. This is a consistent real-life case series that support the use of biologic drugs in patients with TST. Conclusions: IL-23 and IL-17 inhibitors, being immunomodulators rather than immunosuppressants, may be a safe option for patients in an active oncological setting and for immune-correlated adverse events.

Pregnancy in patients affected by axial-spondyloarthritis: a narrative review of disease activity and obstetric outcomes.

This review aims to summarize the most recent and updated data on pregnancy in patients with axial spondyloarthritis (axSpA), focusing on the recurrence of pregnancy-related complications, the disease activity throughout gestation and the postpartum, and the latest indications for the treatments of future mothers. We have conducted a narrative review with an online literature search on Medline and PubMed. We selected only studies written in English published until January 2024, including observational and retrospective studies, meta-analyses, and systematic reviews. Proper preconception counseling and maternal-fetal monitoring are necessary to ensure the best outcome for both the mother and her baby. Despite the limited and conflicting evidence about the prevalence of adverse pregnancy outcomes in women with axSpA compared to healthy controls, primary findings demonstrate an increased risk of preterm delivery (PTD), low birth weight (LBW), and elective cesarean section (CS). Concerning disease activity, data suggests that 25-80% of women with ankylosing spondylitis experience disease flares during pregnancy, particularly around 20 weeks of gestation. On the contrary, the data on the postpartum disease flare are heterogeneous. The use of biological drugs in pregnancy is safe and effective in controlling disease activity. Data on pregnancy outcomes in patients with axSpA are scarce and discordant. Probably the difference in maternal disease classification, the evolution of treatment indications, and the differences emerging from study designs can account for these discrepancies. The main evidence shows an increased risk of PTD, LBW, and elective CS (although the latter may reflect cultural influences rather than medical needs due to axSpA itself). The majority of drugs used to treat axSpA, including TNFi, are safe in pregnancy without harming mothers or fetuses. Further data is needed to clarify many controversial aspects in this area.

Comment on "Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project". [Response to Letter

Comment on "Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project". [Response to Letter

Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Current state and advances in desensitization for peanut allergy in pediatric age.

Peanut allergy affects about 1%-3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4-17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop.

Effectiveness of use of biological drugs and microelements in the cultivation of chickpeakes in light chestnut soils in the Volgograd region

Chickpeas are widespread in countries with arid climates, where they are sown annually on an area of 10–11 million hectares. The favorable combination of protein, fat, carbohydrates, macro- and microelements, vitamins, and biological active substances in grain make it a complete feed for farm animals and poultry. The purpose of the research was to study the eff ectiveness of the use of biological products and microelements when cultivating chickpeas under the conditions of light chestnut soils in the Volgograd region. In the process of work, two series of experiments were carried out: the fi rst – “Pre-sowing treatment of chickpea seeds with microfertilizers” and the second – “Combined use of growth stimulants and microfertilizers”. The most important conditions for the realization of chickpea productivity, taking into account the biological characteristics of the variety Privo 1 in the soil and climatic conditions of light chestnut soils of the Volgograd region have been identifi ed. In the second experiment, the average lowest economic yield of chickpea variety Privo 1 was formed in the control variant without seed treatment with microelements and growth stimulants and was equal to 1,92 t/ha. The highest economic yield of chickpeas, on average, according to experience, was established in combinations of the growth stimulator HB-101 with boric acid or ammonium molybdate during pre-sowing seed treatment and was equal to 2,59 t/ha, i.e. was 34,9 % higher than in the control variant. It was recommended that under the conditions of the Volgograd region on light chestnut soils when cultivating chickpea variety Privo 1, before sowing, treat chickpea seeds with growth stimulant HB-101 (50 ml/t) in combination with ammonium molybdate (NH4)2MoO4 – (250 g/t) or boric acid H3BO3, B(OH)3 (500 g/t). Sowing should be carried out as early as possible with a seeding rate of 500 thousand viable seeds on 1 ha.

Mixed connective tissue disease with juvenile onset: results of a retrospective single-center study

Mixed connective tissue disease (MCTD) is one of the very rare systemic autoimmune diseases; it accounts for 0.1–0.6% of cases in pediatric rheumatologists' practices. MCTD is characterized by a broad spectrum of clinical manifestations and a high frequency of extremely unspecific symptoms at the onset, with the overall picture of the disease forming slowly and gradually. The diagnosis is often delayed and confirmed only at an advanced stage of organ dysfunction with the development of irreversible changes.Objective: to identify a group of patients fulfilling the criteria for MCTD in an open, single-center, continuous retrospective study among anti-ribonucleoprotein (anti-RNP) antibody-positive patients and to analyze their demographic, clinical and laboratory characteristics and therapy.Material and methods. All anti-RNP-positive patients admitted to the pediatric department of V.A. Nasonova Research Institute of Rheumatology from 2019 to 2023 and meeting at least one of the variants of the MCTD criteria (Kasukawa, Alarcуn-Segovia, Kahn and Sharp criteria) were included in the study.Results and discussion. 18 (56.25%, 17 girls and 1 boy) of 32 anti-RNP-positive patients fulfilled criteria for MCTD. Patients most frequently fulfilled a combination of criteria – Sharp and Kahn (n=8) or Alarcуn-Segovia and Kahn (n=8). The median age of onset of MCTD was 12.2 [9.7; 13.9] years. The most common clinical manifestations were arthritis (100%), various skin lesions (94.4 %), Raynaud's phenomenon (88.9%), lymphadenopathy (72.2%) and general constitutional disorders (50%). Sjögren's syndrome (SS) was diagnosed in 17 (94.4%) patients. All patients had antinuclear factor (ANF) 1/1280, and the anti-RNP level was >200 U/ml. There were also antibodies against double-stranded DNA (n=5), Ro- (n=4) and Sm- (n=5) antigens. An IgM rheumatoid factor was detected in 6 patients and hypergammaglobulinemia in 10 patients. Capillaroscopic changes in the nailfold with predominant scleroderma type were found in 77.8% of patients. The most common combination was of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia (50%). All patients received glucocorticoids, 9 – hydroxychloroquine, 8 – methotrexate, 3 – mycophenolate mofetil, 1 – cyclophosphamide, 1 – azathioprine. Biologic DMARDs (bDMARDs) were prescribed to 12 (66.7%) patients: 3 – rituximab, 8 – abatacept, 1 – belimumab, with an acceptable safety profile and initial efficacy.Conclusion. Most patients in the study met the Kahn criteria. Only 2 patients met all variants of the criteria, which indicates the need to use a combination of criteria when a MCTD is suspected. A combination of Raynaud's phenomenon, arthritis, SS, lymphadenopathy and hypergammaglobulinemia was observed in half of patients with MCTD. The presence of Raynaud's phenomenon and high ANF titer in children with rheumatic diseases, especially with a polymorphic clinical picture, requires the inclusion of MCTD in differential diagnosis. Preliminary results indicate the safety of the use of biologic drugs in children with MCTD.

The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives.

Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.

The Application of Peptide Nucleic Acids (PNA) in the Inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Gene Expression in a Cell-Free Transcription/Translation System.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that plays a key role in the metabolism of low-density lipoprotein (LDL) cholesterol. The gain-of-function mutations of the PCSK9 gene lead to a reduced number of surface LDL receptors by binding to them, eventually leading to endosomal degradation. This, in turn, is the culprit of hypercholesterolemia, resulting in accelerated atherogenesis. The modern treatment for hypercholesterolemia encompasses the use of biological drugs against PCSK9, like monoclonal antibodies and gene expression modulators such as inclisiran-a short, interfering RNA (siRNA). Peptide nucleic acid (PNA) is a synthetic analog of nucleic acid that possesses a synthetic peptide skeleton instead of a phosphate-sugar one. This different structure determines the unique properties of PNA (e.g., neutral charge, enzymatic resistance, and an enormously high affinity with complementary DNA and RNA). Therefore, it might be possible to use PNA against PCSK9 in the treatment of hypercholesterolemia. We sought to explore the impact of three selected PNA oligomers on PCSK9 gene expression. Using a cell-free transcription/translation system, we showed that one of the tested PNA strands was able to reduce the PCSK9 gene expression down to 74%, 64%, and 68%, as measured by RT-real-time PCR, Western blot, and HPLC, respectively. This preliminary study shows the high applicability of a cell-free enzymatic environment as an efficient tool in the initial evaluation of biologically active PNA molecules in the field of hypercholesterolemia research. This cell-free approach allows for the omission of the hurdles associated with transmembrane PNA transportation at the early stage of PNA selection.

Vaccinations in Selected Immune-Related Diseases Treated with Biological Drugs and JAK Inhibitors-Literature Review and Statement of Experts from Polish Dermatological Society.

The growing use of biological drugs in immune-mediated chronic diseases has undoubtedly revolutionized their treatment. Yet, the topic of vaccinations in this group of patients still raises many concerns and implies many therapeutic problems that require discussion and standardization of management. The aim of this literature review is to present current knowledge regarding safety and efficacy of vaccinations in dermatological and rheumatological patients treated with biological drugs and JAK inhibitors. Additionally, this article provides recommendation from experts of the Polish Dermatological Society about proper use of vaccinations during therapy with biologics. Generally, all live attenuated vaccines are contraindicated during immunosuppressive/immunomodulatory therapy. If there is need, they should be administered long enough prior to the therapy or after cessation. Yet, inactivated vaccines mostly can be safely used, but the problem in this case is the effectiveness of the vaccination. Most studies report that the immune response in patients on biologics after administration of different inactivated vaccines is similar to or even better than in the control group. Thus, the importance of vaccination among patients on biologics must be emphasized to reduce omissions and the fear of possible side effects or insufficient post-vaccination response.

Comments on "Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project" [Letter

Comments on "Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project" [Letter

Hepatosplenic involvement of tuberculosis: an uncommon presentation that demands attention in specific scenarios.

Abdominal tuberculosis (TB), a potential differential diagnosis for acute and chronic abdomen, should be considered in specific situations, such as immunosuppressant or biological drug use, HIV, or in patients residing in endemic areas. Although the presence of thoracic tuberculosis may indicate abdominal TB, only 15% of patients with abdominal TB have evidence of pulmonary disease. Involvement of the liver and spleen is a common autopsy finding in patients with disseminated TB. However, the most common pattern is of fine miliary lesions. Hepatic involvement with a macronodular pattern, a rare occurrence, is linked to dissemination through the portal vein. The splenic macronodular form, an extremely rare presentation, can manifest as solitary or multiple nodules, oval or round, with a variable appearance reflecting different stages of the disease, adding to the uniqueness of this case.

The impact of anti-tumor necrosis factor alpha drugs on lipid profile of patients with rheumatoid arthritis or seronegative spondyloarthropathy

Background: Inflammatory arthritis is associated with abnormal levels of lipoprotein. The cause is considered to be inflammation. Recently, the use of biologic drugs in the treatment of inflammatory arthritis, especially rheumatoid arthritis (RA) and seronegative spondyloarthropathy, has increased. There are different results of the effect of these drugs on fat profile. Evaluate the impact of anti-tumor necrosis factor (TNF) alpha drugs on lipid profile of patients with RA or seronegative spondyloarthritis. Methods: In this cross-sectional descriptive study, 50 patients with rheumatoid arthritis or seronegative spondyloarthritis, who were candidates for TNF alpha treatment, were included in the study. After obtaining written consent, a checklist was completed for all patients including demographic information such as age, sex, height, weight, place of residence, level of education, type of disease, and lipid profile test results including total cholesterol, triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were recorded. Then the patients were treated and evaluated for fat profile after 3, 6, 9 months after receiving the relevant treatment regimen. The test results were recorded in checklists. After completing the study, the data were entered into the statistical package for the social sciences (SPSS) 24 software and analyzed. Results: The mean age of patients was 46.38±14.33 years. 54% of patients were female. 54% of patients had rheumatoid arthritis. 62% of patients were treated with Sinora. The results of this study showed that serum triglyceride levels increased during the study period and this increase was statistically significant but the trend of changes in serum cholesterol, HDL and LDL levels was not statistically significant. However, serum LDL levels measured in the ninth month increased significantly compared to the initial measurement. Conclusions: Results showed that there was a significant relationship between lipid profile changes and anti-TNF alpha consumption. Although decreased inflammation appears but other mechanisms may be involved in dyslipidemia.

Results of a non-interventional observational multicenter study of the management of patients with axial psoriatic arthritis in real-life clinical practice (NiSaXPA)

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate-Severe Crohn's Disease: A Systematic Review.

Conventional therapy is the most commonly used treatment for Crohn's disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate-severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate-severe CD in adult patients with an inadequate response or intolerance to conventional therapy.

Risk of Nephrolithiasis in Patients with Inflammatory Bowel Disease Receiving Biologic Treatment.

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract. Biologic drugs target specific molecules in the body's immune system to control inflammation. Recent studies have suggested a potential link between their use and an increased risk of nephrolithiasis. We conducted a study to further investigate this association. The study used multiple logistic regression analysis to assess the association between the use of biologic drugs and nephrolithiasis. A p-value of <0.05 was considered statistically significant. SAS 9.4 was used for statistical analysis. The final sample consisted of 22,895 cases, among which 5603 (24.51%) were receiving at least one biologic drug. The biologic drugs received were as follows: Adalimumab 2437 (10.66%), Infliximab 1996 (8.73%), Vedolizumab 1397 (6.11%), Ustekinumab 1304 (5.70%); Tofacitinib, 308 (1.35%); Certolizumab, 248 (1.08%); and Golimumab, 121 (0.53%). There were 1780 (7.74%) patients with Nephrolithiasis: 438 (8.0%) patients were receiving biologic treatment. We found that the use of Vedolizumab (OR = 1.307, 95% CI 1.076-1.588, p = 0.0071) increased the odds of Nephrolithiasis by 31%. Vedolizumab use was associated with an increased risk of nephrolithiasis. The use of two or more biologic drugs also increased the risk compared to no biologic treatment.

Translated article] Consensus recommendations on the preventive treatment of migraine

ObjectiveThe objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. MethodologyRecommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. ResultsAfter both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). ConclusionsThe high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Microbiota and antibiotic therapy in rhinosinusitis.

Rhinosinusitis is one of the most frequently diagnosed diseases in patients seeking medical consultation. Sinusitis is a heterogeneous group of diseases and can be acute or chronic. The current state of knowledge on rhinosinusitis is presented in the recommendations of the European Position Paper on Rhinosynusitis and Nasal Polyps 2020 (EPOS 2020). More and more attention is paid to the condition of the microbiota in the context of inflammatory changes in the sinuses. There is also a negative effect of excessively prescribed antibiotics on the increase in bacterial resistance to drugs and significant changes in the disturbance in the composition of the microbiota during antibiotic therapy. Since the most common etiology of acute sinusitis is viral, the use of antibiotics in uncomplicated sinusitis is unjustified. New therapeutic solutions are sought, including the use of herbal medicines. The EPOS 2020 document recommends the use of BNO 1016 in uncomplicated acute rhinosinusitis. New models of treatment also take into account the use of biological drugs, especially in the treatment of chronic rhinosinusitis.

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.

Stairway to Heaven: Do head-to-head Trials Indicate a Need for Definite Criteria for Choosing Biologic Drugs in Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic disease characterized by joint and systemic involvement that develops with different pathogenetic mechanisms. Treatment of the disease is undertaken with disease-modifying anti-rheumatic drugs (DMARDs). The mechanisms of action of conventional DMARDs generally are based on the inhibition of T and B-cells in the immune system. In recent years, biologic and targeted smart molecules have been used in the treatment of RA. Targeting different cytokines and inflammatory pathways, these drugs have ushered in a new era in RA treatment. The efficacy of these drugs has been demonstrated in many studies; and in the postmarketing period, that is, as the patients who use them say, they are like a "stairway to heaven". However, as every "road to heaven" is challenging and "thorny", the efficacy and reliability of these drugs and whether any one of them is superior to the others, remains a matter of debate. However, the use of biologic drugs with or without cDMARDs, the preference for original vs. biosimilar molecules, and discontinuation of the drugs after achieving sustained remission are other questions that need to be explored. When it comes to the choice of biological drugs by rheumatologists, it is not yet clear on which criteria they base their choices on. Due to the limited comparative studies of these biological drugs, the subjective criteria of the physician gains importance. The selection of these drugs, however, should be based on objective criteria such as efficacy, safety, superiority over each other, and cost. In other words, the determinant of the "path to heaven" should be based on objective criteria and recommendations according to the scientific data generated by controlledprospective studies, not on the initiative of a single physician. In this review, a head-to-head comparison of biological drugs used in the treatment of RA, their efficacy, safety, and which are superior are discussed in light of recent literature data.