Olokizumab

Last updated

Olokizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from rat)
Target IL6
Clinical data
Trade names Artlegia
Routes of
administration
Subcutaneous
ATC code
Pharmacokinetic data
Elimination half-life 31 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Molar mass 146000 Da
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Olokizumab (OKZ) sold under the name Artlegia, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and COVID-19. It is a humanized monoclonal antibody against the interleukin-6 (IL-6). IL-6 is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases. Olokizumab is the first interleukin-6 (IL-6) inhibitor approved for treatment of rheumatoid arthritis which blocks directly cytokine instead of its receptor. [1] Olokizumab specifically binds to IL-6 at Site 3, blocking IL-6 ability to form hexameric complex. [2] Olokizumab was developed by R-Pharm group, and was launched in 2020. [3]

Contents

Medical uses

Rheumatoid arthritis

Olokizumab was approved for medical use in Russia, [3] Kazakhstan, Belarus, Kirgizstan and Azerbaijan under the brand name Artlegia for treatment of patients aged 18 years or older with moderate to severe rheumatoid arthritis in combination with methotrexate who have an inadequate response to methotrexate or tumor necrosis factor inhibitor (TNFi) therapy. [1] [4]

COVID-19

Olokizumab was approved for pathogenesis-based therapy of cytokine release syndrome in patients with moderate to severe new coronavirus infection (COVID-19) was approved in Russia, [3] Kirgizstan and Azerbaijan.

Contraindications

Drug interactions

In all clinical trials in patients with rheumatoid arthritis, olokizumab was used in conjunction with methotrexate. Special clinical studies of drug interactions of olokizumab have not been conducted. Concomitant use with methotrexate did not affect the olokizumab exposure. The effect of olokizumab on the methotrexate exposure is not expected with their simultaneous use. According to the results of the CREDO1–3 clinical trials, no cases of clinically significant drug interactions of olokizumab with other drugs were reported. In an in vitro study on human cryopreserved hepatocytes, olokizumab reversed the inhibitory effect of IL-6 on CYP1A1/2, 2B6, 2C9, 3A4/5 and 2C19 activity, as well as on NTCP activity. Thus, it should be considered that in patients with active rheumatoid arthritis, dose adjustment of drugs metabolized by these CYP isoforms may be necessary after beginning the treatment with olokizumab.

The concentration of the following drugs may decrease when used together with olokizumab (including, but not limited to): statins (simvastatin, lovastatin, atorvastatin); oral contraceptives; calcium channel blockers; glucocorticoids (dexamethasone, methylprednisolone); warfarin; quinidine; theophylline; tizanidine; phenytoin; pimozide; cyclosporine; sirolimus; tacrolimus; benzodiazepines (e.g., diazepam, alprazolam, triazolam, midazolam, bromazepam).

History

Olokizumab efficacy and safety were studied as part of a large-scale program of clinical trials, CREDO, which included 2,444 adult patients with rheumatoid arthritis from 19 countries worldwide. The study of olokizumab continues in the general, open-label, long-term extension.

CREDO 1. Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy. [5] [6]

CREDO 2. Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy. [7] [8]

CREDO 3. Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy. [9] [6]

CREDO 4. Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis. [10]

Related Research Articles

<span class="mw-page-title-main">Disease-modifying antirheumatic drug</span> Category of drugs

Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal anti-inflammatory drugs and steroids.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

<span class="mw-page-title-main">Belimumab</span> Pharmaceutical drug

Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States and Canada, and the European Union to treat systemic lupus erythematosus and lupus nephritis.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Briakinumab (ABT-874) is a human monoclonal antibody being developed by Abbott Laboratories for the treatment of rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. As of 2011 drug development for psoriasis has been discontinued in the U.S. and Europe.

<span class="mw-page-title-main">Tofacitinib</span> Medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

Sirukumab is a human monoclonal antibody designed for the treatment of rheumatoid arthritis. It acts against the proinflammatory cytokine Interleukin 6 (IL-6).

Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.

Namilumab is a human monoclonal antibody that targets granulocyte macrophage-colony stimulating factor (GM-CSF)/colony stimulating factor 2 (CSF2) and is currently being researched for application in rheumatoid arthritis (RA) and psoriatic arthritis. Clinical trials investigating the therapeutic utility of Namilumab have include phase I and phase II clinical trials to establish the safety, tolerability and preliminary therapeutic utility of the antibody in plaque psoriasis and rheumatoid arthritis.

<span class="mw-page-title-main">Gemigliptin</span> Chemical compound

Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.

<span class="mw-page-title-main">Baricitinib</span> Chemical compound

Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.

Guselkumab, sold under the brand name Tremfya, is a monoclonal antibody against interleukin-23 used for the treatment of plaque psoriasis, psoriatic arthritis, and ulcerative colitis.

<span class="mw-page-title-main">Filgotinib</span> Chemical compound

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

Vobarilizumab is a humanized bispecific nanobody designed for the treatment of inflammatory autoimmune diseases.

<span class="mw-page-title-main">Upadacitinib</span> Biopharmaceutical drug

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

<span class="mw-page-title-main">Abrocitinib</span> Chemical compound

Abrocitinib, sold under the brand name Cibinqo, is a medication used for the treatment of atopic dermatitis (eczema). It is a Janus kinase inhibitor and it was developed by Pfizer. It is taken by mouth.

<span class="mw-page-title-main">Josef Smolen</span> Austrian rheumatologist and immunologist (born 1950)

Josef Smolen is an Austrian rheumatologist and immunologist and professor emeritus at the Medical University of Vienna. Since 2018, he is chairman emeritus of the Department of Internal Medicine 3 and the Division of Rheumatology at the Medical University of Vienna and Vienna General Hospital and was the chairman of the 2nd Medical Department and Center for Diagnosis and Therapy of Rheumatic Diseases at the Lainz Hospital, now the Hietzing Clinic of the Vienna Health Association from 1989 to 2017.

References

  1. 1 2 Abuelazm M, Ghanem A, Mahmoud A, Brakat AM, Elzeftawy MA, Mamdouh Fayoud A, et al. (June 2023). "The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis". Clinical Rheumatology. 42 (6): 1503–1520. doi:10.1007/s10067-023-06519-6. PMC   10202974 . PMID   36792848.
  2. Nasonov EL, Feist E (2022-11-10). "Перспективы ингибиции интерлейкина-6 при ревматоидном артрите: олокизумаб (новые моноклональные антитела к ИЛ-6)" [The prospects of interleukin-6 inhibition in rheumatoid arthritis: Olokizumab (novel monoclonal antibodies to IL-6)]. Rheumatology Science and Practice (in Russian). 60 (5): 505–518. doi: 10.47360/1995-4484-2022-505-518 . ISSN   1995-4492.
  3. 1 2 3 "Государственный реестр лекарственных средств" [State register of medicinal products]. grls.rosminzdrav.ru (in Russian). Retrieved 2024-04-01.
  4. Mahmoud AM (2023). "Olokizumab's Effectiveness and Safety in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials". Journal of Clinical Densitometry. 26 (1): 61–82. doi:10.1016/j.jocd.2022.12.003. PMID   36535857.
  5. Clinical trial number NCT02760368 for "A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy" at ClinicalTrials.gov
  6. 1 2 Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, et al. (December 2022). "Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study". Annals of the Rheumatic Diseases. 81 (12): 1661–1668. doi:10.1136/ard-2022-222630. PMC   9664111 . PMID   36109142.
  7. Clinical trial number NCT02760407 for "A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy" at ClinicalTrials.gov
  8. Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, et al. (August 2022). "Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis". The New England Journal of Medicine. 387 (8): 715–726. doi:10.1056/NEJMoa2201302. PMID   36001712.
  9. Clinical trial number NCT02760433 for "A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy" at ClinicalTrials.gov
  10. Clinical trial number NCT03120949 for "A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis" at ClinicalTrials.gov