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Cureus May 2024Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies...
Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies that have been developed to treat the disease's symptoms. However, some patients still do not find relief with these medications and turn to other therapies such as diet modification. The underlying cause of Crohn's disease involves multiple factors such as uncontrolled inflammation and several genetic variants. While most current medication therapies control the symptoms that occur due to this uncontrolled level of inflammation, an anti-inflammatory diet (AID) may actually lower the level of inflammation in the gut and therefore reduce the amount of disease symptoms in Crohn's disease. Some such diets include the IBD-AID, Crohn's disease exclusion diet, and the Groningen AID (GrAID). This report describes a case of treatment-resistant Crohn's disease in a patient who was given all categories of pharmaceutical therapies including prednisone, budesonide, sulfasalazine, olsalazine, 6-mercaptopurine, methotrexate, mesalamine, and adalimumab. These only gave temporary relief of symptoms and eventually failed for various reasons including allergic reaction, insufficient symptom control, and antibody formation against the medication. This prompted the patient to independently research AIDs instead. In conclusion, for patients whose disease is refractory to different treatments, or who develop antibodies to the medication, AIDs may offer a solution to reduce disease symptoms and progression. Education of healthcare professionals and patients alike is vital in order for Crohn's patients to gain the benefits from dietary therapy.
PubMed: 38939280
DOI: 10.7759/cureus.61262 -
Cureus May 2024Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on...
Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).
PubMed: 38939259
DOI: 10.7759/cureus.61264 -
Przeglad Gastroenterologiczny 2024Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels...
INTRODUCTION
Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels remains a mystery.
AIM
We analysed whether the drugs used in the treatment of IBD patients could affect the concentration of SARS-CoV-2 antibodies.
MATERIAL AND METHODS
This is a prospective, single-centre evaluation of the persistence of SARS-CoV-2 antibodies after vaccination at various time points: every 2 months throughout the 6 month after the first dose.
RESULTS
We included a total of 346 vaccinated IBD patients in the study. A negative correlation between antibody level and time from full vaccination was confirmed for the following types of therapy: infliximab (rho = -0.32, < 0.001), adalimumab (rho = -0.35, = 0.025), and vedolizumab (rho = -0.50, < 0.001). In the case of other, long-term drug administration, a negative correlation between antibody level and time from full vaccination was confirmed for mesalazine (rho = -0.35, < 0.001), budesonide (rho = -0.58, = 0.004), systemic glucocorticoids (rho = -0.58, < 0.001), and azathioprine (rho = -0.44, < 0.001).
CONCLUSIONS
Due to the immunosuppressive and biological treatment, IBD patients are exposed to a shorter persistence of SARS-CoV-2 antibodies and require booster doses. The role of gastroenterologists in educating patients about the need to continue SARS-CoV-2 vaccination remains crucial.
PubMed: 38939061
DOI: 10.5114/pg.2023.130126 -
Arthritis Care & Research Jun 2024The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic...
OBJECTIVE
The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs).
METHODS
The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM.
RESULTS
Four bDMARD CTPs were proposed: TNF-alpha inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67/72]) as well as for patient characteristics, assessments, outcome measures, and follow up. By weighted average, respondents indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab.
CONCLUSION
CTPs for the use of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.
PubMed: 38937134
DOI: 10.1002/acr.25393 -
The Journal of Investigative Dermatology Jun 2024
PubMed: 38936766
DOI: 10.1016/j.jid.2024.05.020 -
Current Medical Research and Opinion Jun 2024MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in...
MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in healthy volunteers or in patients with psoriasis or rheumatoid arthritis (RA). This is the first study conducted under clinical practice conditions evaluating the switch from reference adalimumab to MSB11022 in patients with RA. Retrospective and multicenter study with data from the medical records of patients with RA who switched from reference adalimumab or another biosimilar to MSB11022 and maintained this treatment for at least 6 months. Information registered comes from baseline visit, the moment of the switch, and the follow-up visits. Data from 86 patients were evaluated (median age 63.5 years, 75.6% female, 44.2% had erosive RA). Only 3.5% of the patients received biologic therapy prior to adalimumab. At baseline, median DAS28-CRP was 1.77 (80.2% in remission and 96.5% with low disease activity) and median CDAI was 4.00 (44.2% in remission and 90.7% with low disease activity). After a median follow-up of 8 months, median DAS28-CRP was 1.87 (86.0% in remission and 94.2% with low disease activity) and median CDAI was 4.00 (38.5% in remission and 95.3% with low disease activity). Only three patients experienced pain, swelling, and stinging at the injection site or a locally extensive hematoma in the area of administration. Adalimumab biosimilar MSB11022 maintained the efficacy benefits provided by previous adalimumab treatments with a safety profile in line with that already described for other biosimilars.
PubMed: 38932718
DOI: 10.1080/03007995.2024.2372295 -
Pharmaceutics Jun 2024The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is...
Single-Cell Transcriptomic and Targeted Genomic Profiling Adjusted for Inflammation and Therapy Bias Reveal and as Novel Hub Genes for Anti-Tumor Necrosis Factor Alpha Therapy Response in Crohn's Disease.
The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found in CD4 T cells and in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.
PubMed: 38931955
DOI: 10.3390/pharmaceutics16060835 -
Pharmaceutics May 2024Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and...
Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.
PubMed: 38931826
DOI: 10.3390/pharmaceutics16060702 -
Biomolecular NMR Assignments Jun 2024Adalimumab is a therapeutic monoclonal antibody developed to target human TNF an important mediator of immune-mediated inflammatory diseases such as rheumatoid...
Adalimumab is a therapeutic monoclonal antibody developed to target human TNF an important mediator of immune-mediated inflammatory diseases such as rheumatoid arthritis, amongst others. The 48 kDa Fab fragment of adalimumab was produced in Escherichia coli using a single chain approach to allow complete isotopic incorporation of deuterium, carbon-13 and nitrogen-15 along with the protonated isoleucine-d, valine and leucine methyl groups. Here we report the near complete resonance assignment of the polypeptide backbone and the methyl groups of isoleucine, leucine and valine residues.
PubMed: 38926254
DOI: 10.1007/s12104-024-10187-1 -
European Journal of Hospital Pharmacy :... Jun 2024In the Danish healthcare system, restructuring is an ongoing process to accommodate the rising number of patients and to optimise resource allocation. To ease...
OBJECTIVES
In the Danish healthcare system, restructuring is an ongoing process to accommodate the rising number of patients and to optimise resource allocation. To ease departmental burdens at hospitals in the North Denmark Region, outpatients are empowered to collect their cost-free medicines from medication pick-up lockers. The lockers function similarly to a package box, thereby enhancing patient freedom. Due to lack of evidence within the published literature regarding cost-free medicines and medicine waste, the aim of our study was to identify the common medications delivered to medicine pick-up lockers and secondly, to evaluate potential medicine waste.
METHODS
Data from ApoVision provided insights into medications delivered to medicine pick-up lockers from March to October 2023 in the North Denmark Region. To estimate unused medicines we obtained data on the number of medications returned from medicine pick-up lockers.
RESULTS
From 2020 to 2023, the number of patients receiving cost-free medicines at medication pick-up lockers increased. In total, approximately 30 000 packages of medicine were delivered to medicine pick-up lockers from March to October 2023 in the North Denmark Region; 1.7% were returned. Methotrexate, adalimumab, and omalizumab were among the most common deliveries and were also the three most returned from the medicine pick-up lockers.
CONCLUSIONS
This study is an initial attempt to investigate potential medicine waste in cost-free medicines dispensed to outpatients via pick-up lockers. Antineoplastic and immunomodulating agents were the most common medicines delivered to medication pick-up lockers in the North Denmark Region from March to October 2023. In this period, approximately 2% of all delivered medicine packages were returned to the hospital pharmacy. Our analysis solely focuses on waste associated with medications left uncollected from medicine pick-up lockers. Addressing the impact of medicine waste in a hospital setting requires a comprehensive approach, thus future studies should also focus on other sites relevant for medication waste as, for example, the patient's household.
PubMed: 38925908
DOI: 10.1136/ejhpharm-2024-004224