Treatment Of Rheumatologic Diseases Research Articles

Evaluation of the readability levels of patient information leaflets of frequently prescribed drugs in rheumatology practice

The development and use of new drugs have accelerated in proportion tothe increase in understanding of the pathogenesis of rheumatological diseases. In the treatment of rheumatological diseases, regular and proper use of drugs prevents disease progression and protects the patient from potential exacerbations and complications. The readability of patient information leaflets (PILs) increases treatment compliance. In this study, it was aimed to evaluate the readability levels of PILs of frequently prescribed drugs in rheumatology practice. A total of 182 frequently prescribed medications in rheumatology practice were randomly selected. The PILs of these drugs were scored according to Ateşman and Bezirci-Yılmaz readability scales and their readability levels were thus determined. It was determined that the PILs could be read with 11-12 years of education and high school education on average according to Ateşman and Bezirci-Yılmaz readability scales respectively. Considering the fact that the mean schooling level in Türkiye is 6.5 years, the readability levels of the PILs of frequently prescribed medications in rheumatology practice are well above this level. It is suggested that the current readability of the PILs is adjusted in accordance with the patients’ level of understanding and education and arrangements to increase the readability levels are made.

PCR106 Certolizumab Pegol Persistence and Adherence By Drug Formulation, in Patients with Axial Spondyloarthritis, Psoriatic Arthritis, or Rheumatoid Arthritis

Adherence to biologic therapy remains a significant problem in the treatment of rheumatologic diseases. This study assessed persistence and adherence associated with certolizumab pegol (CZP), a biologic administered as a lyophilized powder (LYO) in-office or as a prefilled syringe (PFS) administered at home.

A Hydroxychloroquine-Related Acute Severe Liver Disease

Drug-induced liver injury can develop depending on the drug itself, its metabolites or the host immune system. Hydroxychloroquine (HCQ) is used prevalently in the treatment of rheumatological diseases. Severe liver toxicities associated with HCQ have been rarely reported in the literature. We present the case of a 36-year-old female patient who was using HCQ due to adult Still's disease whose initial values were normal but arrived 3 weeks later with severely high liver enzyme and bilirubin levels. The diagnosis of acute severe liver disease due to HCQ use was made by eliminating other causes and conducting a liver biopsy. The patient recovered completely with steroid therapy. It should be kept in mind that HCQ, which was prevalently used worldwide at the beginning of the coronavirus disease-2019 pandemic, can lead to severe liver disease in rare cases.

Prevalence of high-risk human papilloma virus infection and cervical cytological abnormalities in female Turkish patients with rheumatologic disease

Background/Aim: It is believed that patients with rheumatological diseases (RDs) are more prone to infectious diseases, possibly due to both disease-related immune dysfunction and chronic inflammation, and immunosuppressive agents used in the treatment of rheumatological diseases. In this context, we aimed to evaluate the prevalence of high-risk human papillomavirus (Hr-HPV) infection and cervical cytological abnormalities in Turkish female patients with RDs and compare them with healthy controls (HCs). Methods: 362 sexually active patients with RDs followed up between January 2014 and June 2021 were included in this cross-sectional study. Patients with RDs were classified as autoimmune and non-autoimmune groups according to seropositivity. Data of 883 age-matched HCs were used for comparison. Demographic features, cervical cytology reports of the patients and HPV test results were retrieved from hospital database. Cervical cytological abnormalities was categorized according to Bethesda 2014. Cobas assay was used for detecting and typing for Hr-HPV. Results: The RDs group and the HCs group were similar in terms of mean age, BMI, and rate of smokers (P>0.05). Cytological evaluation was carried out in all of 362 patients with RDs (161 autoimmune and 201 non-autoimmune) and in all of 883 HCs. HPV test was applied in 286 patients with RDs and 776 of HCs. 16 (4.4%) patients with RDs and 58 (6.6%) HCs had cervical cytological abnormality. Of the patients who underwent HPV testing; 22 (7.7%) patients with RDs and 75 (9.7%) HCs had Hr-HPV. The prevalence of cervical cytologic abnormalities and Hr-HPV infection rate were similar between patient groups and HCs (P=0.186 and P=0.400, respectively). Conclusion: It was determined that chronic systemic inflammation, which plays a role in the pathogenesis of rheumatological diseases, and immunosuppressive agents used in the treatment did not increase the prevalence of Hr-HPV infection and cervical cytological abnormalities.

Immunosuppression in Rheumatologic and Auto-immune Disease.

Many rheumatologic diseases are thought to originate in dysregulation of the immune system; lupus nephritis, for example, involves humoral immunity, while autoinflammatory diseases such as familial Mediterranean fever are caused by defects in innate immunity. Of note, this dysregulation may involve both upregulation of immune system components and aspects of immunodeficiency. Treatment of rheumatologic diseases thus requires a familiarity with a variety of immunosuppressive medications and their effects on immune system function.In many rheumatologic conditions, due to an incompletely elucidated mechanism of disease, immunosuppression is relatively broad in contrast to agents used, for example, in treatment of transplant rejection. Multiple immunosuppressive drugs may also be used in succession or in combination. As such, an understanding of the mechanisms and targets of immunosuppressive drugs is essential to appreciating their utility and potential adverse effects. Because of the overlap between therapies used in rheumatologic as well as other inflammatory disorders, some of these medications are discussed in other disease processes (e.g., Immunosuppression for inflammatory bowel disease) or in greater detail in other chapters of this textbook (corticosteroids, mTOR inhibitors, antiproliferative agents).

Analysis of adverse drug reactions in the treatment of rheumatological diseases with biological medicinal products – a systematic review of scientific publications

To analyze reports of adverse drug reactions (ADRs) occurring during and after treatment of rheumatologic diseases with biological medicinal products (BMPs), published in the scientific literature; to determine the type, frequency, grade of severity and evaluate the causality with the ongoing treatment. The literature search was conducted in MEDLINE and PubMed databases for the period from November 2002 to November 2016. We found 710 publications, and 225 papers were selected for data extraction. We carried out descriptive and variational analyses as basic statistical analyses. We defined mean values, standard deviation, minimum, maximum, 95% confidence intervals. We assessed the results using PICOS instrument – population, intervention, comparison, outcomes and study design. The analyzed population included 137,564 patients with rheumatic diseases. Original articles and reviews account for the largest share of publications - 183 (81.33%). The most frequently used medicinal products were monoclonal antibodies. We found data of 284 types of ADRs. The most commonly reported ADRs were: common infections, development (activation) of tuberculosis infection, malignancies. ADRs were found in 12,979 patients, i.е. in 9,43% of the population, there was at least one ADR. Our systematic review has shown increased interest in the pharmacovigilance of biological medicinal products. The larger share of scientific publications, however, use non-standardized terminology to describe ADRs, which is not in line with the current pharmacovigilance concept. Ignorance of the notions, inaccurate and incorrect handling of scientific-regulatory terminology, and errors in ADRs reporting and publication in scientific literature do not allow for systematic reviews in this field.

Biologics in rheumatology

Monoclonal antibodies and fusion proteins were introduced into clinical rheumatology 20 years ago. Nowadays they are an established component of modern internal medical practice. This article gives an overview of the breadth of biologics currently in clinical use. Evaluation of published approval studies and guideline recommendations, discussion of the immunological principles and targets in the treatment with biologics. Monoclonal antibodies and fusion proteins for influencing cytokine signals, T‑cell costimulation and B‑cell function are the most important innovations in the treatment of rheumatological diseases. Nowadays they are indispensible for the treatment of moderate and severe disease courses of rheumatoid arthritis, spondylarthropathies and vasculitides. Although a cure or permanent freedom from symptoms in rheumatological autoimmune diseases is still not possible, much more favorable disease courses with less long-term limitations can be achieved by the early administration of biologics.

Corneal thickness and endothelial changes in long-term hydroxychloroquine use

Objective: To determine possible associations between long-term HCQ use and corneal changes in patients who used HCQ for at least 3 years.Materials and methods: The study included 62 healthy controls and 62 consecutive patients who used HCQ for the treatment of rheumatologic disease and were referred to the ophthalmology department between August 2018 and November 2018 for HCQ retinal toxicity screening. Central corneal thickness (CCT), corneal endothelial cell density (ECD), the coefficient of variation (CV) of cell size, and the percentage of hexagonal cells (HEX%) were measured to evaluate changes in the cornea.Results: The mean age of the patient group and control group was 50.10 ± 10.91 and 50.53 ± 10.67 years, respectively. The mean ECD was 2742 ± 347 (cells/mm2) in the patient group and 2875 ± 188 cells/mm2 in the control group. There was a significant difference between groups (p = 0.01). The mean CCT was 567.05 ± 32.35 µm in the patient group and 540.15 ± 38.50 µm in the control group. CCT was significantly higher in the patient group compared with control group (p < 0.001). There was no significant difference between groups in terms of mean CV and HEX values (p > 0.05).Conclusions: Patients using long-term HCQ demonstrated lower ECD and higher CCT than the control group. However, the CV of cell sizes and the HEX % values were not significantly different from the controls.

Ultrasound of the knee in rheumatology

The knee joint, surrounding ligaments, and extensor mechanism (quadriceps and patellar tendon), given their superficial nature, are easily accessible and accurately assessed with high-resolution musculoskeletal (MSK) ultrasound. Its bedside availability, lower cost than magnetic resonance imaging (MRI), and its high sensitivity in the detection of a small effusion, synovitis, and Baker's cyst, together with its ability to be used for needle guidance in invasive procedures, make ultrasound a highly desired diagnostic tool. In this article, we will focus on common rheumatologic indications of MSK ultrasound in the knee and discuss scanning technique and sonographic findings. Transducer positioning and essential sonographic bony landmarks will be reviewed and scanning in two orthogonal planes (both long and short axis of the structure) will be emphasized. With advances in technology, cost reduction, and easy availability, it is expected that more and more clinicians will be utilizing ultrasound in their clinics in management and treatment of rheumatologic diseases. The diagnostic ability of MSK ultrasound is based on an operator's training and experience, the patient's habitus and aptly chosen clinical indications. A good grasp of anatomy, sound ultrasound technique, and knowledge of limitations of ultrasound modality is essential for a safe ultrasound practice. It is also important to keep in mind that ultrasound provides limited information about internal structures such as meniscus and cruciate ligament pathologies and it has a complementary role with MRI.

Arthropathy in Dermatology: A Comprehensive Review.

Dermatology and rheumatology are two specialties that deal with significant overlap. In this context, it is important that the dermatologists acquaint themselves with conditions presenting with arthropathy. As the first step, it is essential to know whether the origin of musculoskeletal symptom is articular or extra-articular; inflammatory or noninflammatory; acute or chronic; oligo- or poly-articular. This will help in narrowing down the differential diagnoses as well as in better correlation with the cutaneous symptoms. In this review, we discuss the skin and articular manifestations of common inflammatory and noninflammatory arthropathies including rheumatoid arthritis, spondyloarthropathies, connective tissue disorders, vasculitis, crystal arthropathies, infective arthritis, arthritis associated with degenerative, endocrine and metabolic conditions, etc. We have also added a section on the common cutaneous features associated with the treatment of rheumatologic diseases. A basic understanding of the joint pathologies and associated skin changes will help a long way in the better management of these conditions.

Three cases of anti-TNF induced myositis and literature review

Anti-tumor necrosis factor drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti-tumor necrosis factor drugs is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti-tumor necrosis factor drugs and review the current literature. We report two cases of rheumatoid arthritis and a case of ankylosing spondylitis developed idiopathic inflammatory myopathy following anti-tumor necrosis factor therapy. In conclusion, myositis could develop during anti-tumor necrosis factor therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.

Três casos de miosite induzida pelo anti‐TNF e revisão da literatura

Anti‐tumor necrosis factor (anti‐TNF) drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti‐TNF is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti‐TNF and review the current literature. We report two cases of rheumatoid arthritis (RA) and a case of ankylosing spondylitis (AS) developed idiopathic inflammatory myopathy following anti‐TNF therapy. In conclusion, myositis could develop during anti‐TNF therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.

Efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study.

The biosimilar of infliximab, CT-P13, has recently been shown to be equivalent to infliximab in both efficacy and safety in the treatment of rheumatologic diseases. However, no data are available with respect to the drug's efficacy in patients with inflammatory bowel disease (IBD). We aimed to assess the efficacy and safety of CT-P13 in IBD patients This was a retrospective multicenter study including both anti-tumor necrosis factor (TNF) naïve patients and patients who switched from the biologic originator to CT-P13. In anti-TNF naïve Crohn's disease (CD) patients (n = 32), clinical response and remission rates were 90.6% and 68.8% at week 2, 90.6% and 84.4% at week 8, 95.5% and 77.3% at week 30, and 87.5% and 75.0% at week 54, respectively. In anti-TNF naïve ulcerative colitis (UC) patients (n = 42), clinical response and remission rates were 76.2% and 19.0% at week 2, 81.0% and 38.1% at week 8, 91.3% and 47.8% at week 30, and 100% and 50.0% at week 54, respectively, while mucosal healing rates were 58.3% at week 8, 66.7% at week 30, and 66.7% at week 54. The efficacy of CT-P13 was maintained in 92.6% (25/27) of CD patients and in 66.7% (6/9) of UC patients after switching from its originator. Adverse events related to CT-P13 occurred in 11.8% of UC patients. CT-P13 appears to have comparable efficacy, safety, and interchangeability with its originator in the treatment of IBD. Further prospective studies with long-term follow-up periods will be needed to confirm the biosimilarity of CT-P13.

Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis

BackgroundMicroglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. MethodsWe activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. ResultsHCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. ConclusionHCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS.

Finding a place for interleukin-1 inhibitors in the treatment of rheumatologic diseases.

Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.

Emerging and reemerging neurologic infections.

The list of emerging and reemerging pathogens that cause neurologic disease is expanding. Various factors, including population growth and a rise in international travel, have contributed to the spread of pathogens to previously nonendemic regions. Recent advances in diagnostic methods have led to the identification of novel pathogens responsible for infections of the central nervous system. Furthermore, new issues have arisen surrounding established infections, particularly in an increasingly immunocompromised population due to advances in the treatment of rheumatologic disease and in transplant medicine.

Expert Panel Recommendations for the Use of Anti–Tumor Necrosis Factor Biologic Agents in Patients with Ocular Inflammatory Disorders

To provide recommendations for the use of anti-tumor necrosis factor α (TNF-α) biologic agents in patients with ocular inflammatory disorders. Ocular inflammatory diseases remain a leading cause of vision loss worldwide. Anti-TNF-α agents are used widely in treatment of rheumatologic diseases. A committee of the American Uveitis Society performed a systematic review of literature to generate guidelines for use of these agents in ocular inflammatory conditions. A systematic review of published studies was performed. Recommendations were generated using the Grading of Recommendations Assessment, Development, and Evaluation group criteria. Numerous studies including controlled clinical trials have demonstrated that anti-TNF-α biologic agents (in particular infliximab and adalimumab) are effective in the treatment of severe ocular inflammatory disease. Based on these studies, the expert panel makes the following recommendations. Infliximab and adalimumab can be considered as first-line immunomodulatory agents for the treatment of ocular manifestations of Behçet's disease. Infliximab and adalimumab can be considered as second-line immunomodulatory agents for the treatment of uveitis associated with juvenile arthritis. Infliximab and adalimumab can be considered as potential second-line immunomodulatory agents for the treatment of severe ocular inflammatory conditions including posterior uveitis, panuveitis, severe uveitis associated with seronegative spondyloarthropathy, and scleritis in patients requiring immunomodulation in patients who have failed or who are not candidates for antimetabolite or calcineurin inhibitor immunomodulation. Infliximab and adalimumab can be considered in these patients in preference to etanercept, which seems to be associated with lower rates of treatment success.

Adverse effects of golimumab in the treatment of rheumatologic diseases

Introduction: A number of new biological immune modulators have become available as treatments for inflammatory diseases over the past two decades. Most prominent among them are TNF-α inhibitors (TNFi) which have been available in the clinic since the late 1990s. TNFi have demonstrated efficacy in various rheumatologic diseases as well as in inflammatory bowel disease and psoriasis. Golimumab is one of the most recently introduced TNFi.Areas covered: Although golimumab is generally well tolerated, as is the case with other TNFi and indeed with most of the marketed immunomodulatory drugs, potential adverse events may be associated with its use. Herein, we the potential adverse effects associated with golimumab therapy are reviewed. Adverse effects are divided into target-related and agent-related categories.Expert opinion: Golimumab has been demonstrated to be generally safe and well tolerated. Its safety profile seems to be very comparable to the other available TNFi. Long-term studies of golimumab and other TNFi will help establish the durability of response to golimumab as well as identify any potential delayed or cumulative adverse effects.

Update in Rheumatology: Evidence Published in 2012

This Update summarizes studies published in 2012 that the authors consider highly relevant to the practice of rheumatology. Topics include treatment of rheumatologic disease, pharmacoepidemiology, ...

Early retinal and retinal nerve fiber layer effects of hydroxychloroquine: a follow up study by sdOCT

Context: The antimalarial drug hydroxychloroquine (HCQ), used in the treatment of rheumatologic disease, has been associated with the development of retinopathy. The long-term incidence of HCQ retinopathy has been estimated at 0.5% when recommended dosages (≤6.5 mg/kg per day) are used.Objective: Evaluating the patients for whom HCQ treatment will be started before and after treatment prospectively with spectral domain (sd) optical coherence tomography (OCT) to observe possible early changes in the retinal and retinal nerve fiber layer thickness.Materials and methods: Thirty-six patients from rheumatology clinic who have been started HCQ therapy had clinical examination and sdOCT imaging before and 6 months after starting treatment. The baseline ophthalmological examinations and visual field analysis (on automated Humphrey visual field (HVF) 10-2 perimetry, Humphrey HFA II-i 750 i, Carl Zeiss Meditec AG, Jena, Germany) were completely normal. The sdOCT was performed with the Optovue technology according to the manufacturer’s guidelines using EMM5, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) scans. The retinal thickness values in central foveal, inferior and superior hemispheres, temporal, superior, nasal and inferior para- and perifoveal areas and the RNFL thickness of eyes were compared before and 6 months after starting treatment by the paired t test.Results: The retinal thickness values in central parafoveal (p = 0.02), and superior hemisphere (p = 0.01) in parafoveal area, parafoveal superior (p = 0.02), temporal (p = 0.03) and nasal (p = 0.04) quadrants were significantly thicker after 6 months of treatment. The thickness of the perifoveal area and the average RNFL thickness was not significantly different in any of the quadrants before and after starting HCQ treatment. The GCC thickness also did not change significantly different in superior and inferior hemisphere after starting treatment.Discussion and conclusion: We observe increased retinal thickness in parafoveal areas in patients on HCQ therapy at short term. Its clinical significance may be apparent in longer follow up studies.