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International Journal of Infectious... Jun 2024Yellow fever (YF) is a potentially lethal viral hemorrhagic fever that can be prevented with the 17D live attenuated YF vaccine. However, this vaccination can cause...
Yellow fever (YF) is a potentially lethal viral hemorrhagic fever that can be prevented with the 17D live attenuated YF vaccine. However, this vaccination can cause severe adverse reactions including vaccine-associated YF. Here, we describe the case of a 32-year-old female who was permanently immunosuppressed with an anti-CD20 antibody due to multiple sclerosis. Following YF vaccination, the patient developed a variety of symptoms such as febrile temperatures, muscle and joint pain, headaches, and dysuria. A vaccine-associated YF with viremia was diagnosed. To avoid a potentially severe course of the disease, sofosbuvir was used as antiviral treatment followed by the resolution of symptoms and serological response. As travelers with chronic diseases and immunosuppression will increasingly engage in long distance travel, this case demonstrates the importance of assessing patient history prior to the administration of live vaccines and points towards a possible therapeutic approach in those suffering from vaccine-associated YF.
Topics: Adult; Female; Humans; Antiviral Agents; Immunocompromised Host; Rituximab; Sofosbuvir; Yellow Fever; Yellow Fever Vaccine; Antigens, CD20; Multiple Sclerosis
PubMed: 38521450
DOI: 10.1016/j.ijid.2024.107017 -
Skin Research and Technology : Official... Mar 2024
Topics: Humans; Scalp; Nails; Psoriasis; Antibodies, Monoclonal, Humanized; Nail Diseases
PubMed: 38509841
DOI: 10.1111/srt.13662 -
Clinical Lymphoma, Myeloma & Leukemia Jun 2024Advancements in frontline therapy and chemotherapy-sparing treatments in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have altered the treatment...
BACKGROUND
Advancements in frontline therapy and chemotherapy-sparing treatments in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have altered the treatment algorithms of this disease. We present a frontline alternative for treatment- naïve (TN) CLL/SLL patients.
METHODS
This was a single-center, phase 2 study of high-dose methylprednisolone (HDMP) and ofatumumab with lenalidomide and ofatumumab consolidative therapy for all comers with TN CLL/SLL. Treatment was continued until disease progression or intolerable side effects. Patients were assessed for response per iwCLL 2008 criteria after completing cycles 3 and 12.
RESULTS
Forty-five patients were enrolled (median age, 62.6 years). High-risk features included del17p (18%), Del11q (22%), and unmutated IGHV gene (76%). Median treatment duration was 32·2 (2·7-75·9) months. Thirty-six patients discontinued treatment due to disease progression (22%), adverse events (40%), allogeneic hematopoietic cell transplantation (allo-HCT) (7%), consent withdrawal (4%), and secondary malignancies (7%). The best overall and complete response rates were 96& and 29% respectively. At median follow-up of 61·7 (5·6-84·9) months, 9 patients remained on treatment. Median progression-free survival was 54·4 (2·9-77·6) months. Three patients underwent allo-HCT after a median of 3 (3-4) treatment cycles. Treatment was well tolerated, with a grade 3/4 infusion reaction in one patient. The most common grade 3/4 hematological adverse event was neutropenia (69%). Four patients had grade 3/4 infections. No grade 3/4 tumor flares, tumor lysis syndrome, or thrombosis were observed.
CONCLUSION
The combination of ofatumumab, HDMP, and lenalidomide was effective and relatively well tolerated in treatment-naive CLL/SLL. Its role in the frontline setting remains unclear given the current available and effective treatment options.
FUNDING
The funders had no role in the study.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide; Middle Aged; Female; Male; Aged; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized; Follow-Up Studies; Methylprednisolone; Adult; Aged, 80 and over; Biomarkers, Tumor
PubMed: 38508880
DOI: 10.1016/j.clml.2024.02.001 -
Frontiers in Neurology 2024Drug-induced liver injury (DILI) is a potential adverse event of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS), as well as of...
Drug-induced liver injury (DILI) is a potential adverse event of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS), as well as of methylprednisolone pulsed therapy used in case of MS relapse. DILI may be induced by different mechanisms, including idiosyncratic reaction, autoimmune hepatitis or viral reactivation. In patients receiving the humanized anti-CD20 monoclonal antibody (mAb) ocrelizumab, DILI has been rarely reported and was mostly associated with hepatitis B virus (HBV) reactivation. Here we present the case of a woman with highly active relapsing-remitting MS who had experienced two episodes of DILI while receiving different DMTs, and was successfully switched to ofatumumab, a fully human anti-CD20 mAb, after a further event associated with ocrelizumab treatment and unrelated to HBV reactivation. Despite sharing the mechanism of action, differences in structure, pharmacokinetic/pharmacodynamic profile, and use of ancillary drugs (only needed for ocrelizumab) may have accounted for the successful switch. To our knowledge, this is the first report of a successful switch from ocrelizumab to ofatumumab due to DILI. Ofatumumab may therefore represent a valid therapeutic option for patients experiencing DMTs- and ocrelizumab-induced liver injury, providing that HBV reactivation has been ruled out.
PubMed: 38487332
DOI: 10.3389/fneur.2024.1363493 -
Drugs Mar 2024Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab,... (Review)
Review
Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed the therapeutic landscape of MS through robust efficacy on clinical manifestations and MRI lesion activity, and the currently available anti-CD20 mAb therapies for use in MS are a cornerstone of highly effective disease-modifying treatment. Ocrelizumab is currently the only therapy with regulatory approval for primary progressive MS. There are currently few data regarding the relative efficacy of these therapies, though several clinical trials are ongoing. Safety concerns applicable to this class of therapeutics relate primarily to immunogenicity and mechanism of action, and include infusion-related or injection-related reactions, development of hypogammaglobulinemia (leading to increased infection and malignancy risk), and decreased vaccine response. Exploration of alternative dose/dosing schedules might be an effective strategy for mitigating these risks. Future development of biosimilar medications might make these therapies more readily available. Although anti-CD20 mAb therapies have led to significant improvements in disease outcomes, CNS-penetrant therapies are still needed to more effectively address the compartmentalized inflammation thought to play an important role in disability progression.
Topics: Humans; Multiple Sclerosis; Rituximab; Antigens, CD20
PubMed: 38480630
DOI: 10.1007/s40265-024-02011-w -
Frontiers in Immunology 2024This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic... (Meta-Analysis)
Meta-Analysis
AIM
This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic syndrome (FRSDNS).
METHODS
We conducted systematic searches of PubMed, Embase, the Cochrane Library, and the Web of Science up to May 23, 2023. Outcome measures included relapses within 1 year, mean cumulative exposure to corticosteroids, patients with treatment failure at 1 year, relapse-free survival during 1 year, and adverse events. The quality of the included studies was evaluated using the modified Jadad scale, the Methodological Index for Non-Randomized Studies (MINORS), and the modified Newcastle-Ottawa Scale (NOS).
RESULTS
Rituximab was found to be the most likely (92.44%) to be associated with the fewest relapses within 1 year and was also most likely (99.99%) to result in the lowest mean cumulative exposure to corticosteroids. Rituximab had the highest likelihood (45.98%) of being associated with the smallest number of patients experiencing treatment failure at 1 year. CsA was most likely (57.93%) to achieve the highest relapse-free survival during 1 year, followed by tacrolimus (26.47%) and rituximab (30.48%). Rituximab showed no association with serious side effects and had comparable adverse effects to ofatumumab and tacrolimus.
CONCLUSION
Rituximab may be the most favorable immunosuppressive agent for treating pediatric FRSDNS. Nephrologists should consider this drug, along with their clinical experience, patient characteristics, and cost considerations, when choosing a treatment approach.
Topics: Child; Humans; Glucocorticoids; Immunosuppressive Agents; Nephrotic Syndrome; Network Meta-Analysis; Recurrence; Rituximab; Steroids; Tacrolimus
PubMed: 38464533
DOI: 10.3389/fimmu.2024.1310032 -
Frontiers in Immunology 2024Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and...
Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×10 IU/ml in serum and 4.48×10 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.
Topics: Humans; Female; Adult; Neuromyelitis Optica; Hepatitis B virus; Aquaporin 4; Antibodies, Monoclonal, Humanized
PubMed: 38426084
DOI: 10.3389/fimmu.2024.1351782 -
Frontiers in Immunology 2024To assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical...
OBJECTIVE
To assess the effect of B cell depletion therapy (BCDT) on circulating T follicular helper (cTfh) and circulating T helper 17 (cTh17) cells and its relation to clinical improvement in patients with myasthenia gravis (MG).
METHODS
28 anti-AchR positive MG patients treated with ofatumumab and 28 healthy controls (HCs) were included. Frequencies of cTfh and cTh17 cells were monitored by flow cytometry at baseline and 4, and 12 weeks after the initial dose ofatumumab. Serum cytokines associated with cTfh and cTh17, including IL-6, IL-21, and IL-17, were also analyzed.
RESULTS
The frequency of cTfh and cTh17 significantly increased in MG patients compared with HCs. Additionally, elevated levels of both T-cell subsets correlated with MG severity. During the follow-up, cTfh and cTh17 return to normal after BCDT. Furthermore, the decrease in cTfh and cTh17 was associated with MG scores improvement over time. Notably, cTfh- and cTh17-related cytokines, including IL-6, IL-21, and IL-17, exhibited a marked decrease following ofatumumab therapy.
CONCLUSIONS
Abnormal expansion of cTfh and cTh17 cells may be key features in the immunopathology of MG. Their levels returned to normal after BCDT, which was closely correlated with clinical amelioration. This result suggests that these two T-cell subsets may be targets for BCDT treatment of MG.
Topics: Humans; Interleukin-17; Interleukin-6; Th17 Cells; Cytokines; Myasthenia Gravis; Antibodies, Monoclonal, Humanized
PubMed: 38415260
DOI: 10.3389/fimmu.2024.1280029 -
Diseases (Basel, Switzerland) Feb 2024Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma...
Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (mAb), may be an effective treatment in this population. Real-world data on PAT effectiveness are limited. To evaluate response to PAT measured through 90-day all-cause morbidity and mortality, we performed a retrospective review of patients who contracted COVID-19 within a year from the last BCDT. From 64 included patients, the majority were Caucasians (95%), female (56%), vaccinated (67%), treated outpatients (64%), with multiple comorbidities. Examined BCDT were rituximab (55%), obinutuzumab (33%), ocrelizumab (11%) and ofatumumab (1%), used for underlying hematological malignancy (HEM) (40%), multiple sclerosis (34%), and rheumatoid arthritis (16%). Of seven deceased patients, three died from COVID-19. All three were elderly males with multiple comorbidities, treated inpatient for severe COVID-19. Four of 41 patients treated as outpatients were hospitalized for non-COVID-19-related reasons. All deceased and hospitalized patients had an underlying HEM. All but one were on rituximab. PAT may be an effective treatment for patients receiving BCDT, especially if given early for non-severe disease. Patients with underlying HEM may be at increased risk for severe disease compared with others receiving the same BCDT.
PubMed: 38391780
DOI: 10.3390/diseases12020033 -
Human Vaccines & Immunotherapeutics Dec 2024Booster vaccinations against SARS-CoV-2 are recommended 6-12 months after the last dose or infection in elderly and high-risk groups. The present analysis aims to...
Booster vaccinations against SARS-CoV-2 are recommended 6-12 months after the last dose or infection in elderly and high-risk groups. The present analysis aims to evaluate whether an interval shorter than 12 months is required in multiple sclerosis patients receiving ofatumumab. Neutralizing antibody status over 1 year in patients receiving booster vaccination in the non-interventional, multicenter KYRIOS study under continued ofatumumab treatment was analyzed. Fifteen patients were included. At the time of the first booster vaccination, ten patients were seropositive for neutralizing antibodies, four patients were seronegative, and for one patient, no baseline levels were available. All patients who were seropositive at baseline showed >2-fold increase in neutralizing antibody titers after the first booster and two patients (20%) showed a >10-fold increase. Among seronegative patients, three (75%) had a >10-fold increase in neutralizing antibody titers. Seropositivity was maintained in almost all patients until month 12. One initially seronegative patient had less than 2-fold increase in neutralizing antibody titers after the booster vaccination and can be considered a non-responder. Most patients with continued ofatumumab treatment are able to maintain permanent seropositivity and therefore presumably constant protection against severe courses of COVID-19 if repeated booster vaccinations are applied.
Topics: Aged; Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Multiple Sclerosis; mRNA Vaccines; Antibodies, Neutralizing; Antibodies, Viral; Vaccination; Antibodies, Monoclonal, Humanized
PubMed: 38346223
DOI: 10.1080/21645515.2024.2316422