Safety and Effectiveness of Combination Rituximab and Cyclophosphamide Therapy for Treating Pediatric Patients With Severe Manifestations of Rheumatic Disease

Infliximab and Azathioprine for Crohn's Disease: A Super-Sonic Combination?

Background:Hydroxyurea therapy is crucial in managing sickle cell disease (SCD) in pediatric patients, significantly reducing vaso-occlusive events. However, it is associated with hematological adverse drug reactions (HADRs), necessitating comprehensive evaluation to ensure patient safety and treatment optimization.Objective:The primary goal of our study is to investigate the prevalence, causality, severity, preventability, and predictability of HADRs associated with hydroxyurea therapy in pediatric patients with SCD.Materials and Methods:A prospective observational study was conducted, involving 207 pediatric SCD patients undergoing hydroxyurea therapy. Data were collected from medical records and adverse drug reaction reporting forms. Causality, severity, preventability, and predictability assessments were conducted using standardized tools.Results:The prevalence of HADRs was 7.24%, with neutropenia (2.41%) and thrombocytopenia (1.93%) being the most common. Gender-specific prevalence rates, age distribution, and in-patient versus out-patient settings showed consistent patterns. Causality assessment revealed a high proportion of probable or certain HADRs. The majority of HADRs were of mild to moderate severity and considered preventable.Finding:Hydroxyurea therapy in pediatric SCD patients is associated with manageable HADRs, emphasizing the importance of pharmacovigilance for patient safety and treatment compliance.Conclusion:This study offers significant insights into the prevalence, clinical management, and outcomes of HADRs associated with hydroxyurea therapy in pediatric SCD patients. The findings underscore the need for proactive management approaches to optimize treatment outcomes and ensure patient safety.

Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences

Optimizing PEG-interferon and ribavirin combination therapy for patients infected with HCV-2 or HCV-3: is the puzzle completed?

Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021 guideline. However, the efficacy of RTX vs. CYC-based treatments in IMN is still controversial. We performed this systemic review and meta-analysis registered in PROSPERO (CRD 42,022,355,717) by pooling data from randomized controlled trials or cohort studies in IMN patients using the EMBASE, PubMed, and Cochrane libraries (till Orc 1, 2022). The primary outcomes were the complete remission (CR) rate + partial remission (PR) rate. CR rate, immunologic response rate, relapse rate, and the risk of serious adverse events (SAE) were secondary outcomes. Eight studies involving 600 adult patients with IMN were included with a median follow-up duration of 12 to 60 months. RTX induced a similar overall remission rate compared with CYC (RR 0.88, 95% CI: 0.71, 1.09, P = 0.23). At the follow-up time of 6 months, RTX was associated with a lower CR + PR rate compared with CYC (RR 0.67, 95% CI: 0.52, 0.88, P = 0.003). Moreover, RTX might be less effective in inducing CR + PR than CYC treatment in IMN patients with high antiPLA2R antibody levels (RR 0.67, 95% CI: 0.48, 0.94, P = 0.02). The occurrences of CRs, relapse rates, immunologic response rates, and SAE were not significantly different between RTX and CYC, respectively. In conclusion, although the long-term efficacy and safety of CYC compared to RTX were comparable, CYC might respond faster and be more advantageous in IMN patients with high antiPLA2R antibody titers.

ObjectiveSevere flare of systemic lupus erythematosus (SLE) often requires aggressive immunosuppressive treatment. The success of the induction treatment is crucial in preventing organ damage. Our aim was to compare the...

A Novel Immunomodulatory Treatment Involving Mycophenolate Mofetil and Corticosteroids for Pediatric Autoimmune Cytopenias

Adefovir (ADV) sequential monotherapy was included in the 2005 Asia-Pacific guidelines for the management of patients with lamivudine (LAM) resistance. However, following the development of ADV resistance, the proportion of resistant variants during combined rescue therapy with ADV and entecavir (ETV) were unknown. The present study characterized the dynamics of resistant variants in patients with chronic hepatitis B (CHB) and LAM-resistant variants during antiviral therapy consisting of ADV monotherapy followed by ADV-ETV combination therapy. A total of 3 patients were selected from a cohort of 55 patients with CHB due to developing ADV resistance. The patients had been previously treated with LAM (100 mg daily) for 21–24 months. At the initiation of sequential monotherapy with ADV, LAM-resistant variants (rtM204V/I and rtL180M) were detected in the three patients. These patients developed ADV resistance during 19–30 months of ADV sequential monotherapy, and then switched their antiviral regimen to ADV-ETV combination therapy. During ADV monotherapy and ADV-ETV combination therapy, the patients were monitored every 3 months for the first year of therapy, and then every 6 months thereafter. A total of 30 serum samples were collected from the patients throughout the monitoring period. In total, 10 mutants that were associated with commonly-used antiviral drugs were detected by pyrosequencing. During ADV sequential monotherapy, LAM-resistant variants were gradually decreased, whereas ADV-resistant rtA181V/T and rtN236T variants gradually increased in the viral population. During 30–41 months of ADV-ETV combination therapy, viral load reduction was 2.59–3.28 log10 copies/ml; ADV-resistant variants rtA181T/V and rtN236T were undetectable following 11–24 months of combination therapy; and rtL180M and rtM204I/V remained dominant in the viral population. In conclusion, the results of the present study suggested that, in patients with LAM and ADV-resistant variants that developed during LAM-ADV sequential monotherapy, ETV-ADV combination therapy may partially inhibit the replication of HBV DNA; however, LAM-resistant rtL180M and rtM204I/V variants remained predominant following 30–41 months combination therapy.

Background:Accurate and rapid diagnosis of rheumatic joint diseases is essential for further treatment decision. Early treatment initiation of different rheumatic diseases slows the progression and positively influence their courses [1-3]....

Background Little data are available concerning the outcome of rituximab (RTX) therapy in pediatric patients with autoimmune bullous diseases (AIBDs). Objective We sought to evaluate safety and efficacy of RTX administration in pediatric patients with AIBDs and to assess first-line RTX therapy in pemphigus patients. Methods AIBD patients consisting of 12 pemphigus patients and a patient with bullous pemphigoid who received RTX before the age of 18 were enrolled. Detailed information regarding patients’ outcome after the first RTX cycle was assessed. Results The mean age of the patients at RTX infusion was 15 ± 2 years. Six patients in the pemphigus group received RTX as first-line therapy. In pemphigus patients: complete remission (on minimal therapy) was achieved by seven patients, partial remission (on minimal therapy) and complete remission (off therapy) were achieved by three patients and one, respectively. Relapse occurred in nine patients, which were mostly mild. Likewise, the BP patient received RTX with a good clinical response. The observed adverse events were mostly mild infusion reactions and a case of sepsis. Conclusion Rituximab is safe and effective in childhood/juvenile patients with AIBDs. Furthermore, RTX can be used as first-line treatment in pediatric patients with pemphigus.

Withdrawal of Immunomodulators or TNF Antagonists in Patients With Inflammatory Bowel Diseases in Remission on Combination Therapy: A Systematic Review and Meta-analysis

BackgroundLupus Low Disease Activity State (LLDAS) permits serological activity and activity in several organs including joint, muscle, and mucocutaneous activity, provided SLEDA4-2K is <=4 and other LLDAS criteria are met.MethodsPatients...

Benefits of Aquatic Therapy in Pediatric Patients with Sickle Cell Disease

Background: The chronic, systemic inflammation in rheumatic diseases can impair male fertility by direct effects on the gonads or by affecting the hypothalamic-pituitary-gonadal (HPG) axis resulting in hypogonadism. Impaired gonadal function is reflected by reduced sperm quality and sometimes lowered testosterone levels. Drugs may impair fertility by impairing spermatogenesis or interfere with the HPG axis. Objectives: To summarize the knowledge on the impact of rheumatic disease and its therapy on fertility in adult and pediatric patients Methods: Search of the literature Results: No impairment of spermatogenesis has been shown for azathioprine, cyclosporine, and mycophenolate mofetil. Risk of permanent infertility is associated with cytotoxic drugs, particularly the alkylating agent cyclophosphamide. Effects of methotrexate (MTX) on male fertility are related to dose. There is no indication that low-dose MTX 5 – 25 mg/week impairs male fertility. Case reports of men with psoriasis treated with low-dose MTX have either found completely normal sperm quality or detected oligo- and azoospermia. Cyclophosphamide (CYC) is administered to adult and pediatric patients with systemic lupus erythematosus, other connective tissue disease and vasculitides. Gonadal damage by CYC is dose-dependent revealed by oligo-and azoospermia as well as low testosterone, low inhibin B and elevated FSH levels. Cumulative doses of > 7.5g/m2 carry a high risk of permanent infertility in adults. In survivors of childhood cancer treated with CYC recovery of spermatogenesis was sometimes seen after many years. Sulfasalazine (SZ) can induce transient infertility with oligospermia, abnormal morphology of sperm cells and reduced sperm motility in about 40-86% of treated men. Plasma levels of steroids and gonadotropins remain normal during SZ therapy. Recovery of normal sperm quality is observed one to three months after discontinuation of SZ. Studies comparing men treated with TNF inhibitors (TNFi) with disease-matched and/or healthy controls did not find impairment of sperm quality neither after short term or long-term treatment. Several studies found significantly better sperm quality in patients receiving long-term TNFi therapy than untreated disease matched controls. Conclusion: Rheumatic disease has an impact on male fertility both by the disease process and by therapy. Most antirheumatic drugs have no negative effect on reproduction, however, treatment with cyclophosphamide increases the risk of infertility both in adults and pediatric patients. Increasing awareness about reproduction issues and infertility risk is needed among adult and pediatric rheumatologists. Clinicians should actively involve themselves in counseling their patients.

Background The gold-standard for prescribing Infliximab (IFX) in IBD is to use it in combination with an immunomodulator (IMM), thereby reducing the risk of immunogenicity and improving overall outcomes. This practice, however, comes with considerable increased risk of adverse events. There is mounting evidence that withdrawal of IMMs, especially after 6 months of combination therapy (CT), does not reduce IFX trough levels or increase the risk of loss of response (Drobne et al., 2015; Mahmoud et al., 2022). We identified IBD patients on IFX CT who were eligible to stop their IMM based on defined criteria and assessed clinical outcomes of patients who had previously had their IMM withdrawn. Methods This was a retrospective cross-sectional study in a central London tertiary hospital. We included patients with a diagnosis of Crohn’s Disease (CD), Ulcerative Colitis, or Indeterminate colitis, with therapeutic IFX levels &amp;gt;5mg/ml, undetectable anti-drug antibodies (ADA) (&amp;lt;10 AU/ml) and at least 6 months of CT from induction between January 2017 and December 2021. Patients were identified on an immunology laboratory database and electronic patient records were manually assessed for baseline characteristics and clinical outcomes. The primary timepoint of interest for clinical outcomes is 4 months after measurement of IFX drug levels. Results A total of 825 IBD patients had IFX drug levels performed in the defined time-period. 296 patients had IFX levels &amp;gt;5mg/ml and undetectable ADAs; of these 160 (54%) had been on CT for &amp;gt;6 months. Baseline characteristics were 41.3% (n=66) female, mean age (y) of 29 (SD ±14) and 70.6% (n=113) had CD. In the 4 months after IFX drug assays, 140 of 160 (87.5%) patients remained on CT whereas 20 (12.5%) had previously stopped their IMM. Of those on CT, 90.7% (127/140) were in clinical remission at the time of the assay compared to 90% (18/20) of patients in the IMM withdrawal group (p=0.46). At the time of data collection, 79.3% (111/140) of CT patients remained on IFX therapy compared to 75% (15/20) who withdrew IMMs (p=0.33, median follow up 19 months). IMM withdrawal was predominantly due to side effects (n=16, 80%) with the remainder due to clinical remission (n=4, 20%). The 2/20 (10%) patients with active disease in the IMM withdrawal group were active prior to stopping IMMs. Conclusion Patients with good IFX drug levels and undetectable ADAs after at least 6 months of IFX CT did well regardless of whether they withdrew IMMs or not, supporting recent studies that suggest it is safe to do so. Given the number of our patients who could potentially benefit from stopping their IMMs, prospective controlled studies are required to determine whether this is advisable given the theoretical risk of loss of response.