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Frontiers in Immunology 2023Alterations in the composition or function of the gut microbiota are associated with the etiology of human diseases. Drug-microbiota interactions can affect drug... (Review)
Review
Alterations in the composition or function of the gut microbiota are associated with the etiology of human diseases. Drug-microbiota interactions can affect drug bioavailability, effectiveness, and toxicity through various routes. For instance, the direct effect of microbial enzymes on drugs can either boost or diminish their efficacy. Thus, considering its wide range of metabolic capabilities, the gut microbiota is a promising target for pharmacological modulation. Furthermore, drugs can alter the microbiota and the mechanisms by which they interact with their host. Individual variances in microbial profiles can also contribute to the different host responses to various drugs. However, the influence of interactions between the gut microbiota and drugs on treatment efficacy remains poorly elucidated. In this review, we will discuss the impact of microbiota dysbiosis in the pathogenesis of rheumatoid arthritis (RA), and we will attempt to elucidate the crosstalk between the gut microbiota and disease-modifying anti-rheumatic drugs (DMARDs), with an emphasis on how drug-microbiota interactions affect the treatment efficacy in RA. We speculate that improved knowledge of these critical interactions will facilitate the development of novel therapeutic options that use microbial markers for predicting or optimizing treatment outcomes.
Topics: Humans; Gastrointestinal Microbiome; Arthritis, Rheumatoid; Antirheumatic Agents; Microbiota; Treatment Outcome
PubMed: 37841256
DOI: 10.3389/fimmu.2023.1189036 -
The Journal of Rheumatology Jul 2024To report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT. (Randomized Controlled Trial)
Randomized Controlled Trial
Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT).
OBJECTIVE
To report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT.
METHODS
Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to UPA 15 mg once daily (QD), UPA 30 mg QD, or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA 15 mg QD or UPA 30 mg QD in the LTE; UPA-randomized patients continued their original dose. Blinding remained until dose switching from UPA 30 mg QD to UPA 15 mg QD because of approval of UPA 15 mg QD; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years.
RESULTS
Overall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued the study drug by 5 years, primarily because of adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved Disease Activity Score in 28 joints based on C-reactive protein < 2.6 among those initially randomized to UPA 15 mg QD and UPA 30 mg QD, respectively. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to UPA or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding nonmelanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed.
CONCLUSION
The 5-year benefit-risk profile for UPA in RA remains favorable. (SELECT-NEXT; ClinicalTrials.gov: NCT02675426).
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Female; Middle Aged; Heterocyclic Compounds, 3-Ring; Male; Treatment Outcome; Adult; Aged; Double-Blind Method; Dose-Response Relationship, Drug
PubMed: 38621793
DOI: 10.3899/jrheum.2023-1062 -
Current Opinion in Rheumatology May 2021Several new therapeutic drugs are now available for the management of rheumatoid arthritis (RA). Given that RA has been associated with an increased risk of certain... (Review)
Review
PURPOSE OF REVIEW
Several new therapeutic drugs are now available for the management of rheumatoid arthritis (RA). Given that RA has been associated with an increased risk of certain cancers like lymphoma and lung cancer, concern remains about the safety of (newer) immunosuppressants used in RA management as it relates to the risk of cancer.
RECENT FINDINGS
Most meta-analyses of randomized clinical trials of tumor necrosis factor inhibitors (TNFi) have not observed an association between TNFi and risk of incident cancer. Studies of non-TNFi biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs and cancer are also reassuring but limited and of short-term follow-up. Regarding the use of DMARDs in patients with RA and a prior malignancy, retrospective studies have shown that TNFi use is not associated with recurrence.
SUMMARY
There is a need for ongoing studies on the safety of non-TNFi bDMARDs and targeted synthetic disease modifying anti-rheumatic drugs and recurrent cancer. Further research is also needed to guide the patients, rheumatologists, and oncologists regarding the safest DMARDs to choose for patients with RA and a recent diagnosis of cancer.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Humans; Neoplasm Recurrence, Local; Neoplasms; Tumor Necrosis Factor Inhibitors
PubMed: 33741804
DOI: 10.1097/BOR.0000000000000796 -
La Revue Du Praticien Nov 2022
Topics: Humans; Janus Kinase Inhibitors; Rheumatology; Antirheumatic Agents; Arthritis, Rheumatoid
PubMed: 36512005
DOI: No ID Found -
Current Opinion in Rheumatology Sep 2019The present review highlights the advances in disease outcome achieved with currently available biologic medications and future perspectives for JIA management. (Review)
Review
PURPOSE OF REVIEW
The present review highlights the advances in disease outcome achieved with currently available biologic medications and future perspectives for JIA management.
RECENT FINDINGS
In the last two decades, the management of juvenile idiopathic arthritis (JIA) has been revolutionized by appropriate legislative initiatives, the existence of very large collaborative networks and the increased availability of the novel biologic medications.
SUMMARY
A more rational approach to the management of JIA is being fostered by the recent publication of therapeutic recommendations, consensus treatment plans and for a treat-to-target strategy.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Child; Consensus; Humans
PubMed: 31169547
DOI: 10.1097/BOR.0000000000000632 -
Advances in Therapy Sep 2020Caring for women in the postnatal period can be challenging. One of the most important aspects is ensuring disease control as there is a risk of flare in the postpartum... (Review)
Review
Caring for women in the postnatal period can be challenging. One of the most important aspects is ensuring disease control as there is a risk of flare in the postpartum period. Other aspects of care also need to be addressed with the mother in mind such as breastfeeding or with the neonate in mind such as vaccinations or complications of the maternal condition affecting the neonate. This article highlights aspects of care that need to be addressed in the postpartum period such as flare rates, maternal wellbeing, thromboembolism, vaccinations, contraception and breast feeding.
Topics: Adult; Aftercare; Antirheumatic Agents; Breast Feeding; Contraception; Female; Humans; Infant, Newborn; Postnatal Care; Postpartum Period; Pregnancy; Rheumatic Diseases; Risk Factors
PubMed: 32729009
DOI: 10.1007/s12325-020-01448-1 -
Nature Reviews. Rheumatology Jul 2023
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid
PubMed: 37217610
DOI: 10.1038/s41584-023-00983-9 -
American Family Physician May 2023
Topics: Humans; Cheek; Arthritis, Rheumatoid; Antirheumatic Agents; Neck
PubMed: 37192083
DOI: No ID Found -
Toxicology Jun 2021Methotrexate (MTX) is one of the most effective and widely used drugs in the management of autoimmune and dermatological diseases. Rheumatoid arthritis and psoriasis... (Review)
Review
Methotrexate (MTX) is one of the most effective and widely used drugs in the management of autoimmune and dermatological diseases. Rheumatoid arthritis and psoriasis patients who are under long term MTX-therapy are at high risk of developing a liver injury. Accumulation of intracellular MTX-polyglutamate (MTX-PG), a metabolite of MTX triggers oxidative stress, inflammation, steatosis, fibrosis, and apoptosis in hepatocytes. MTX-PG causes oxidative stress in the liver by inducing lipid peroxidation thereby releasing reactive oxygen species and suppressing antioxidant response elements. MTX-PG induces several pro-inflammatory signaling pathways and cytokines such as tumor necrosis factor-α, nuclear factor kappa B and interleukin 6 (IL-6), IL- β1, IL-12. MTX-PG depletes hepatic folate level and decreases RNA and DNA synthesis leading to hepatocyte death. MTX-PG inhibits 5-aminoimidazole-4-carboxamide ribonucleotide transformylase enzyme and thereby causes accumulation of intracellular adenosine, which causes activation of hepatic stellate cells, extracellular matrix accumulation and hepatic fibrosis. MTX-PG induces hepatocytes apoptosis by activation of caspase 3 via the intrinsic pathway. Clinically, aggravation of underlying fatty liver to non-alcoholic steatohepatitis with fibrosis seems to be an important mechanism of liver injury in MTX-treated RA patients. Therefore, there is a need for monitoring liver injury in RA, psoriatic and cancer patients with NAFLD and fibrosis risk factors during MTX treatment. This review summarizes the possible molecular mechanism of MTX-induced hepatotoxicity. It may pave the way for early detection of liver injury and develop novel strategies for treating MTX mediated hepatotoxicity.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Chemical and Drug Induced Liver Injury; Dermatologic Agents; Humans; Methotrexate; Psoriasis
PubMed: 34175381
DOI: 10.1016/j.tox.2021.152840 -
Clinical and Experimental Rheumatology 2019A disease-modifying osteoarthritis drug (DMOAD) is a drug that modifies the underlying OA pathophysiology and potentially inhibits the structural damage to prevent or... (Review)
Review
A disease-modifying osteoarthritis drug (DMOAD) is a drug that modifies the underlying OA pathophysiology and potentially inhibits the structural damage to prevent or reduce long-term disability with potential symptomatic relief. The focus of this narrative review is on describing the state of the field for disease-modifying pharmacologic agents that are in late-stage development-specifically phase 2/3.
Topics: Antirheumatic Agents; Biological Products; Humans; Osteoarthritis
PubMed: 31621568
DOI: No ID Found