Pharmacotherapy Options in Rheumatoid Arthritis: Focus on Tocilizumab, a Recombinant Humanized Anti-Interleukin-6 Receptor Antibody

Ohsugi, Yoshiyuki; Kishimoto, Tadamitsu

doi:10.4137/cmt.s2048

Cited by 3 publications

(4 citation statements)

References 80 publications

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“…Some malignant tumors including MPM secrete IL-6, a multifunctional cytokine 13 that may play a crucial role in resistance to chemotherapy or hormonal therapy, 14 as it might be involved in angiogenesis via expression of vascular endothelial growth factor (VEGF), promote establishment of metastatic tumors, 15 and cause cachexia. 16 …”

Section: Discussionmentioning

confidence: 99%

Granulocyte‐colony stimulating factor (G‐CSF) producing malignant pleural mesothelioma: Report of a case

et al. 2015

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This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony-stimulating factor (G-CSF) that was treated by tumor resection. A 76-year-old male presented with a huge right-side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/μL) and C-reactive protein level (20.57 mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and histopathological analysis led to a diagnosis of sarcomatous type of MPM. Immunohistochemical findings for both anti-human G-CSF and interleukin-6 monoclonal antibodies were positive. Although the general condition of the patient quickly improved after surgery, local recurrence occurred two months later and he died of respiratory failure seven months after the operation, though surgery provided symptom relief. G-CSF-producing MPMs usually show a poor prognosis, though less-invasive surgery may be considered for relief of symptoms.

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Section: Discussionmentioning

confidence: 99%

Granulocyte‐colony stimulating factor (G‐CSF) producing malignant pleural mesothelioma: Report of a case

et al. 2015

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“…TCZ inhibits the binding of IL-6 to IL-6R and thus blocks IL-6 signaling in cells. The serum IL-6 level is closely related to disease activity in RA patients, and many of the local and systemic symptoms and signs of RA can be attributed to the overproduction of IL-6 70 .…”

Section: Il-1 Receptor Antagonistmentioning

confidence: 99%

Untitled

2011

IJPSR

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Rheumatoid arthritis (RA) is an aggressive disease that needs to be treated effectively if subsequent deformity and disability are to be reduced. A recent advance in the management of RA is the use of biological agents which block certain key molecules involved in the pathogenesis of the illness. They include tumor necrosis factor (TNF-) -blocking agents, Anti-Interleukin-1receptor (IL-1) antagonist, anti-CD-20 agents, CTLA-4 Ig, anti IL-6 etc. These newer agents proved to be useful for alleviating symptoms and slowing the disease progression in the patients with RA who have failed to respond to conventional disease modifying anti-rheumatic drugs (DMARDs). DMARDs are nonspecific immunomodulators, each of which has substantial drawbacks in terms of effectiveness or adverse effects (AEs). The development of biologic agents has provided more effective therapeutic options. The terms biologic therapies and biologics have emerged to describe agents with biologic properties, including monoclonal antibodies and soluble cytokine receptors etc. The advent of effective biological agents has certainly been a major advance in the treatment of inflammatory arthritis, heralding a new era for rheumatology. In this review the focus is only on pathophysiology of the disease process as well as the recent advances with Biological response modifiers (BRMs) and its impact on current clinical practice in the treatment of RA.

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“…Sarilumab is an immunoglobulin G1 (IgG1) human monoclonal antibody that blocks IL‐6 from binding to the alpha subunit of mIL‐6R and sIL‐6R (sIL‐6Rα), thereby inhibiting IL‐6‐mediated cis‐ and trans‐signaling 8‐11 . Tocilizumab is a humanized IgG1 monoclonal antibody that also blocks IL‐6 from binding to mIL‐6R and sIL‐6Rα 12 . Both sarilumab and tocilizumab are approved for the treatment of adults with moderately to severely active RA 13‐16 .…”

mentioning

confidence: 99%

“…[8][9][10][11] Tocilizumab is a humanized IgG1 monoclonal antibody that also blocks IL-6 from binding to mIL-6R and sIL-6Rα. 12 Both sarilumab and tocilizumab are approved for the treatment of adults with moderately to severely active RA. [13][14][15][16] Decreased absolute neutrophil count (ANC) appears to be a function of inhibiting IL-6 signaling.…”

mentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single‐Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate

Paccaly

Kovalenko

Parrino

et al. 2020

The Journal of Clinical Pharma

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We assessed pharmacokinetics (PK), pharmacodynamics (PD), and PK/PD relationships of interleukin-6 (IL-6), soluble IL-6 receptor, and C-reactive protein (CRP) in serum, and absolute neutrophil count (ANC) in blood following single doses of subcutaneous sarilumab versus intravenous tocilizumab (NCT02097524) from patients with rheumatoid arthritis (RA) who are inadequate responders to methotrexate (MTX) and on a stable dose of MTX. Patients with RA randomized (1:1:1:1) to single-dose sarilumab (150 or 200 mg subcutaneously) or tocilizumab (4 or 8 mg/kg intravenously) were included (n = 101), and PK, PD, and PK/PD relationships and safety were assessed over 6 weeks postdose. PK profiles for both drugs are described by parallel linear and nonlinear target-mediated clearance pathways. PD markers showed similar onset of effect during the first week postdose, regardless of dose or route of administration. CRP and ANC decreased, with median postdose nadirs at 7-15 days for CRP and 3-5 days for ANC. Both drugs at low and high doses achieved the same nadir for ANC and a similar return toward baseline within 2 weeks postdose, suggesting a saturation of effect. Safety profiles of sarilumab and tocilizumab were generally similar. In conclusion, despite differences in PK, the onset of the decrease in CRP (efficacy) and ANC (safety) after a single dose were similar for subcutaneous sarilumab and intravenous tocilizumab. PD effects and safety were consistent with previous studies.

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Pharmacotherapy Options in Rheumatoid Arthritis: Focus on Tocilizumab, a Recombinant Humanized Anti-Interleukin-6 Receptor Antibody

Cited by 3 publications

References 80 publications

Granulocyte‐colony stimulating factor (G‐CSF) producing malignant pleural mesothelioma: Report of a case

Granulocyte‐colony stimulating factor (G‐CSF) producing malignant pleural mesothelioma: Report of a case

Untitled

Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single‐Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate

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