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Immune-Related Adverse Events from Cancer Immunotherapy
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Rheumatic irAEs are notable as they may carry an ongoing burden for patients even after ICI cessation (as in the case with ICI-arthritis) or can co-occur with a more critical irAE (as in the case of ICI-myositis presenting with ICI-myocarditis).30, 45 Recommendations for corticosteroid-sparing agents to consider for ICI-arthritis include, but are not limited to, the following disease-modifying antirheumatic drugs (DMARDs): hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, tocilizumab, TNF-α inhibitors, and consideration of rituximab based on severity.34, 85, 87 Steroid-sparing treatments for ICI-myositis include use of intravenous gammaglobulin (especially if synchronous myasthenia gravis or myocarditis onset) with or without immunosuppression with agents such as mycophenolate mofetil, azathioprine, tacrolimus, or rituximab.26, 46 The immunomodulatory drug of choice should ultimately depend on severity, comorbidities, and whether or not the patient is on an ICI clinical trial that may limit the use of certain immunosuppressive medications.34 In fact, clinical trials often limit use of various immunosuppressive medications and systemic corticosteroids greater than or equal to prednisone 10 milligrams per day for the concern for abrogation of antitumor immunity.1, 3, 9, 13, 14, 19
Antipsychotic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Harleen Kaur, Ramneek Kaur, Varsha Rani, Kanishka Sharma, Pawan Kumar Maurya
Supplementary treatment of schizophrenia with celecoxib has positive effects when treated with risperidone (Geddes et al., 2000). Also, treatment alongside immunomodulatory drug resulted to be helpful for dealing with the symptoms of schizophrenia indicating dysfunction of the immune system. It is associated to pathomechanism and is not just an epiphenomenon. The effect of celecoxib which is a nonimmunological therapeutic is mediated by the receptor of NMDA. Risperidone is considered to be well-established and a proven drug for the treatment of schizophrenia (Müller et al., 2002). The addition of celecoxib has a high impact in improvement of patients suffering from both negative and positive symptoms of schizophrenia (Miller et al., 2011).
Benign Oral and Dental Disease
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Konrad S. Staines, Alexander Crighton
As aphthous ulcers are driven by an immunological reaction, the process can be controlled using immunomodulatory therapy. In some cases, altering environmental factors such as avoiding sodium lauryl sulphate (SLS) containing toothpastes or dietary triggers (benzoate, chocolate, cinnamon) can reduce the triggering of lesions to a level low enough to satisfy the patient. In others, the use of topical immunosuppressants or immunomodulators can successfully alter the clinical course of the disease. As the immunological damage happens some days before the ulcer appears, it is critical that the treatment is started as soon as the patient becomes aware of the lesion. By the time the ulcer appears, it is too late for an immunomodulatory drug to be effective and the patient must rely on analgesic solutions or obturative pastes to manage their symptoms. Treatment options for aphthous ulcers are listed in Table 42.10. Systemic immunotherapy should only be used by a specialist with appropriate experience.
Non-human primates in the PKPD evaluation of biologics: Needs and options to reduce, refine, and replace. A BioSafe White Paper
Published in mAbs, 2022
Karelle Ménochet, Hongbin Yu, Bonnie Wang, Jay Tibbitts, Cheng-Pang Hsu, Amrita V. Kamath, Wolfgang F. Richter, Andreas Baumann
Despite these challenges, investigators are looking at ways to allow NHP re-use, as is described in the human anti-IL17 antibody example. In addition, Hey et al. describe a decision tree used to determine if NHPs previously dosed with a biotherapeutic can be reused.88 Animals that have been treated with an immunomodulatory drug have exhibited irreversible pathological or immunological changes, or have measurable drug concentrations or pharmacologic effects persisting from a previous study are excluded from re-use. A three-month washout is considered standard but may be adjusted accordingly depending on the circumstances. Non-naïve animals are excluded from GLP toxicology studies due to existing uncertainties about potential residual effects of previous treatment. Animals that pass the above criteria can be included in small molecule, non-terminal studies (e.g., PK, PKPD, safety pharmacology) without further screening. If the intended use is for evaluation of biotherapeutics, then animals are further screened using a generic ADA assay. If they are found to be negative, they can be used for non-terminal biotherapeutic studies, including those evaluating PK, PKPD, mechanistic, tolerability (including local tolerance), and also for some terminal non-GLP toxicology studies (e.g., dose range finding studies).
GDF15: a potential therapeutic target for type 1 diabetes
Published in Expert Opinion on Therapeutic Targets, 2022
Soumyadeep Sarkar, John T. Melchior, Hayden R. Henry, Farooq Syed, Raghavendra G. Mirmira, Ernesto S. Nakayasu, Thomas O. Metz
Studies since the early 1980’s suggest that T1D is a multi-stage disease, broadly divided into three major stages and one pre-stage (Figure 3) [70,71]. The pre-stage of T1D is mainly associated with genetic mutation of the HLA gene, triggered by various environmental factors such as β cell mass, β cell stress, pancreatic size, congenital rubella/enterovirus infections, or metabolic stress [72–74]. These factors initiate immune activation and response toward pancreatic β cells. Based on this classification, early treatment strategies have mainly focused on developing anti-inflammatory drugs to treat the onset of T1D, with no long-term success [6,8–10]. Nevertheless, interest in this area persists, as multiple clinical studies are being performed worldwide to develop next-generation immunomodulatory drugs against T1D initiation [6]. Following the trend, GDF15 has been associated with immunosuppressant activity and is regarded as the first anti-inflammatory cytokine to demonstrate regulation of chemokine-triggered leukocyte integrin activation [30,35,75,76]. Therefore, GDF15 could be deemed as a lucrative immunomodulatory target in the future. However, there is a growing paradigm shift in the field regarding T1D pathogenesis. According to the latest consensus, the pancreas is not considered the target of the immune response; and instead, it is regarded as the initiator of immune activation [77,78]. Therefore, this could be a potential rationale for the lack of any successful immunomodulatory drug so far.
Pediatric Uveitis and Scleritis in a Multi-Ethnic Asian Population
Published in Ocular Immunology and Inflammation, 2021
Samanthila Waduthantri, Soon-Phaik Chee
In PS, 66.7% (n = 12) of the cases were idiopathic (Table 2). The most common associations were HLA-B27 haplotype (2, 11.1%) and sarcoidosis (2, 11.1%). The majority had bilateral ocular involvement (13, 72.2%). All cases had persistent inflammation requiring SIT, and 66.7% (n = 12) of the cases required more than one immunomodulatory drug. The mean duration of treatment was 6.59 ± 3.59 years. Three patients (16.7%) were treated with either periocular and/or intravitreal steroid injections in addition to SIT. One patient was treated with adalimumab. One patient had cataract surgery. All patients with PS gained a BCVA of 0.3 LogMAR or better upon completion of treatment. Overall, 66.7% (n = 12) of the patients developed secondary complications. The most common complication was glaucoma (7, 38.9%) followed by cataract (4, 22.2%) and cystoid macula edema (3, 16.7%).