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Clinical Pharmacokinetics May 2024Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for...
BACKGROUND AND OBJECTIVE
Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy.
METHODS
A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.
RESULTS
A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state.
CONCLUSION
Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.
Topics: Humans; Pregnancy; Female; Antibodies, Monoclonal; Pregnancy Complications
PubMed: 38583128
DOI: 10.1007/s40262-024-01370-7 -
Skin Health and Disease Apr 2024Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses, and clinically characterised by painful, rapidly...
Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses, and clinically characterised by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Underlying diseases include rheumatoid arthritis, inflammatory bowel disease, haematopoietic malignancy, and aortitis syndrome. However, there was a limited number of cases of concomitant pyoderma gangrenosum and IgA vasculitis. Herein, we report a case presenting persistent large skin wounds as a diagnosis of pyoderma gangrenosum in the setting of IgA cutaneous vasculitis, which was successfully treated by a TNF-α inhibitor. A 67-year-old obese female presented palpable purpura on her lower extremities. A skin biopsy taken from the purpuric eruption showed leukocytoclastic vasculitis with IgA and C3 depositions in the vessel walls of the upper dermis, leading to the diagnosis of IgA vasculitis. Small skin ulcers rapidly expanded in several days, eventually developing perforating skin ulcers with irregular erythematous and violaceous edges on both lower extremities following the tapered oral prednisolone at a dose of 25 mg per day. Based on the clinical manifestation and histological analysis, we diagnosed her skin wound as pyoderma gangrenosum. After the adalimumab administration, the spreading ulceration was dampened, leading to the acceleration of wound epithelialisation.
PubMed: 38577052
DOI: 10.1002/ski2.347 -
Rheumatology and Immunology Research Mar 2024Psoriasis (PsO) and psoriatic arthritis (PsA) are often undertreated and require a multidisciplinary approach. In recent years, patent expiration has allowed the...
BACKGROUND AND OBJECTIVES
Psoriasis (PsO) and psoriatic arthritis (PsA) are often undertreated and require a multidisciplinary approach. In recent years, patent expiration has allowed the introduction of tumor necrosis factor inhibitor (anti-TNF) biosimilars, which have stimulated a significant increase in the use of biological therapies. This article reports the findings of a multidisciplinary approach to achieve a consensus on the use of adalimumab in patients with PsO or PsA.
METHODS
A voting panel of 36 Italian dermatologists and rheumatologists were chosen by eight Italian clinicians (the Board), to provide a consensus on the real-world management of PsO and PsA with adalimumab using the Delphi Method, comprising three survey rounds. Twelve statements were defined by the Board and submitted to the panel (rating scale 1-7).
RESULTS
Clinicians reached a wide consensus on the effectiveness (score 6-7: 67%) and long-term efficacy (6-7: 100%) of adalimumab in all clinical forms of PsO and PsA, including pediatric patients (6-7: 85%). Considering cost-effectiveness and safety, adalimumab is suggested as a first-line treatment in patients with enthesitis, predominant peripheral arthritis, axial involvement or associated inflammatory bowel disease (IBD) or uveitis. Adalimumab can be also considered after failure of etanercept (6-7: 94%).
CONCLUSION
Results from this Delphi study clearly show an overall consensus on the use of adalimumab in the management of PsO and PsA, particularly as first-choice for specific subpopulations (uveitis, IBD, hidradenitis suppurativa). Considering the cost-effectiveness of biosimilars within Italy, adalimumab may represent an effective and safe first-line treatment for patients with moderate-to-severe PsO or PsA, and a valid choice for switching after failure.
PubMed: 38571927
DOI: 10.1515/rir-2024-0006 -
Farmacia Hospitalaria : Organo Oficial... Apr 2024Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque...
BACKGROUND
Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce.
METHODS
Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, 5 were directly started on MSB11022, and 9 switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index (HBI) have been usEd.) for Crohn's disease and Mayo Score for Ulcerative Colitis. Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab.
RESULTS
No significant differences were observed in clinical disease activity (P=.317) or biochemical parameters [fecal calprotectin (P=.445) and C-reactive protein P=.661)] after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (P=.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects.
CONCLUSIONS
Between originator adalimumab and biosimilar-start cohorts, no differences were observed, between originator adalimumab and switch cohorts, no significant differences were found either, and with the pre- and post-switch to biosimilar comparison, 2 of the 9 patients experienced AEs after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect (rash) with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.
PubMed: 38570210
DOI: 10.1016/j.farma.2024.01.002 -
PloS One 2024In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot...
AIMS
In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4β7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE).
METHODS
Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes.
RESULTS
Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab.
CONCLUSION
This pilot study demonstrate that dual-band CLE is feasible to detect α4β7- and TNF-expressing cells. Positive α4β7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4β7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.
Topics: Humans; Colitis, Ulcerative; Pilot Projects; Fluorescein-5-isothiocyanate; Biomarkers; Endoscopy, Gastrointestinal; Gastrointestinal Agents; Treatment Outcome; Remission Induction; Antibodies, Monoclonal, Humanized
PubMed: 38564601
DOI: 10.1371/journal.pone.0298313 -
ACG Case Reports Journal Apr 2024Idiopathic granulomatous hepatitis is a rare condition characterized by hepatic granulomas with constitutional symptoms such as recurrent fevers, myalgias, and...
Idiopathic granulomatous hepatitis is a rare condition characterized by hepatic granulomas with constitutional symptoms such as recurrent fevers, myalgias, and hepatosplenomegaly in the absence of infection or inflammatory disorder. Typical treatment and course of this disease consist of a course of steroids with rapid symptom resolution. However, symptoms may recur when steroids are tapered. In these circumstances, azathioprine, methotrexate, infliximab, and adalimumab have demonstrated good response. In this case, we present a patient who developed antidrug antibodies to infliximab and adalimumab and was the first documented case of this disease to be treated with certolizumab pegol. Our case highlights the novel efficacy of certolizumab pegol for idiopathic granulomatous hepatitis and its role in treating idiopathic granulomatous hepatitis with antidrug antibodies.
PubMed: 38560016
DOI: 10.14309/crj.0000000000001310 -
Cell Cycle (Georgetown, Tex.) Feb 2024Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate...
Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 (, dual specificity phosphatase 3 (, dual specificity phosphatase 4 (, mitogen-activated protein kinase 9 (, mitogen-activated protein kinase kinase kinase 2 (, mitogen-activated protein kinase kinase 2 ( MAP kinase-activated protein kinase 2 , also known as in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of , , and , while miR-1275 is implicated in regulating expression. Additionally, miR-382 and miR-3188 are potential regulators of levels, and miR-200-5p is involved in regulating and levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.
Topics: Humans; Lipopolysaccharides; MicroRNAs; Adalimumab; RNA, Messenger; Mitogen-Activated Protein Kinases; HaCaT Cells; Keratinocytes; Gene Expression Profiling; Cell Line
PubMed: 38557266
DOI: 10.1080/15384101.2024.2335051 -
Journal of Gastrointestinal and Liver... Mar 2024
Topics: Humans; Adalimumab; Crohn Disease; Mutation; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 38554426
DOI: 10.15403/jgld-5271 -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Adalimumab; Folliculitis; Treatment Outcome; Scalp Dermatoses; Anti-Inflammatory Agents; Female; Male; Adult
PubMed: 38553282
DOI: 10.1016/j.abd.2024.02.001 -
Clinical Case Reports Apr 2024Adalimumab has become essential for managing various chronic inflammatory diseases, including inflammatory bowel disease (IBD). While hematologic complications of...
Adalimumab has become essential for managing various chronic inflammatory diseases, including inflammatory bowel disease (IBD). While hematologic complications of adalimumab therapy are rare, they can have significant clinical implications. This report highlights the importance of recognizing and monitoring for neutropenia in patients receiving adalimumab treatment. We also describe the potential mechanisms and management strategies for this adverse event.
PubMed: 38550736
DOI: 10.1002/ccr3.8629