Golimumab

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Golimumab
Mass / length primary structure 2 * (214 + 448) = 1324 amino acids (easy + difficult)
149,802-151,064 daltons (agalactosyl / monosialyl)
Secondary to quaternary structure IgG1 (γ 1 , κ) antibody
Identifier
External IDs
Drug information
ATC code L04 AB06
Drug class Immunosuppressants

The drug golimumab (also: CNTO 148) is used to treat rheumatic and inflammatory diseases as well as chronic inflammatory bowel diseases . It is a human monoclonal antibody , the effect of which is based on binding to the human tumor necrosis factor alpha (TNFα). Golimumab was developed by Centocor Inc. and approved in Europe on October 1, 2009. It is marketed in Germany by MSD Sharp & Dohme under the trade name Simponi . The drug requires a prescription.

Mechanism of action

In the context of binding to human tumor necrosis factor alpha (TNFα), golimumab forms high-affinity, stable complexes with both the soluble and membrane-bound bioactive forms of TNFα and thus prevents the binding of TNFα to the corresponding receptors. TNFα is a pro-inflammatory cytokine that plays a key role in the pathogenesis of chronic inflammatory joint diseases. The binding of human TNF by golimumab has been shown to neutralize the TNFα-induced cell surface expression of the adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM) -1 and intercellular cell adhesion molecule (ICAM) -1 by human endothelial cells . In vitro , golimumab also inhibits the TNF-induced release of interleukin (IL) -6 , IL-8 and granulocyte-macrophage-colony-stimulating factor (GM-CSF) by human endothelial cells.

Tolerability and side effects

The most common undesirable effects with golimumab are infection and injection site reactions. In the combined phase 3 studies of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, the most common adverse effect up to week 16 was upper respiratory tract infection (7.2% of those treated with golimumab vs. 5.8% in controls ).

In these studies, 28.3% of golimumab-treated patients vs. 24.7% of placebo patients observed infections by week 16. Serious infections such as pneumonia or tuberculosis were observed by week 16 in 1.4% of the golimumab-treated patients versus 1.3% of the patients in the control groups. Before treatment with golimumab, risk factors for tuberculosis must be clarified, as well as a chest x-ray and a tuberculin skin test . To rule out hepatitis B, it may be useful to clarify before starting therapy in justified cases.

Local reactions at the injection site occurred in 5.8% of the golimumab patients by week 16 (vs. 2.2% in the placebo patients); reddening was most common. These local reactions were mostly mild to moderate and generally did not require drug discontinuation.

application areas

Golimumab is currently approved for the treatment of rheumatoid arthritis , ankylosing spondylitis , psoriatic arthritis and ulcerative colitis .

Treatment with golimumab must be started and supervised by a qualified doctor who has experience in the diagnosis and treatment of the diseases for which golimumab is used. Golimumab is given as a 50 mg injection under the skin on the same day of each month once a month . The doctor may increase the dose to 100 mg in patients who weigh more than 100 kg if they do not respond to treatment after three or four doses . After exercising, patients can self-inject golimumab if their doctor agrees. Patients being treated with golimumab receive a special patient education card that summarizes the information on the safety of the medicine.

Rheumatoid arthritis

Golimumab is approved in the EU in combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients when the response to basic anti- rheumatic therapy (DMARD therapy) including MTX has been inadequate.

The efficacy and safety of golimumab in active RA were investigated in three large randomized , double-blind , placebo- controlled phase III studies in MTX-naïve patients (GO-BEFORE, N = 637) and in MTX failures (GO-FORWARD , N = 444) and in anti-TNF-experienced patients (GO-AFTER, N = 461).

In all studies, golimumab was administered sc once a month at doses of 50 mg or 100 mg. The dosage of 50 mg once a month has shown the best benefit-risk ratio and also corresponds to the approved dosage.

The approval-relevant study GO-FORWARD ( GOlimumab FOR subjects With Active RA Despite MTX ) included patients with active RA who had not responded adequately to methotrexate (MTX). The combination of golimumab + MTX led to a significant improvement in symptoms and disease activity and was found to be significantly superior to MTX monotherapy in this regard. The improvements could already be observed at the first measurement point four weeks after the first golimumab injection and continued over the course of time. In addition, there was a significant improvement in physical function and quality of life, as well as fatigue symptoms.

GO-AFTER ( GOlimumab After Former anti-TNF Therapy Evaluated in RA ) is the first prospective phase III study in which RA patients previously treated with TNFα blockers received a different TNFα blocker. In these RA patients, some of whom had previously been treated with several TNFα antagonists, there were significant improvements in clinical symptoms and physical functions as well as a statistically significant reduction in disease activity after they were treated with golimumab. The success of the therapy was sustained over the observation period of six months and was independent of the type and number of previously administered TNFα blockers ( adalimumab , etanercept or infliximab ) or the reason for discontinuing this therapy.

The GO-BEFORE study ( GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid Arthritis of Early onset ) included patients with active RA who had not been previously treated with MTX. There was no statistically significant improvement in joint symptoms or disease activity in the patients treated with golimumab + MTX.

ankylosing spondylitis

Golimumab is approved in the EU for the treatment of severe, active ankylosing spondylitis (AS) in adult patients who have had an inadequate response to conventional therapy.

The efficacy and safety of golimumab in AS were investigated in the Phase III clinical trial GO-RAISE ( GOlimumab - A Randomized Study in Ankylosing Spondylitis Subjects of a Novel Anti-TNF mAB Injection [SC] Given Every Four Weeks ). Treatment with golimumab resulted in a significant improvement in symptoms and physical function.

Psoriatic arthritis

Golimumab is approved in the EU for use as monotherapy or in combination with MTX for the treatment of active and progressive psoriatic arthritis (PsA) in adult patients when the response to previous basic anti- rheumatic therapy (DMARD) has been inadequate.

In the phase III study GO-REVEAL ( GOlimumab - A Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody ) the tolerability and efficacy of golimumab were tested in patients with active PsA. Both the effects on the joints and on the psoriatic skin changes associated with the disease (in patients with skin involvement ≥ 3% of the body surface) and nail changes were recorded.

In the patients treated with golimumab there was a significant improvement in joint symptoms as well as skin and nail changes, with golimumab therapy also proving to be significantly superior to placebo with regard to all criteria for an improvement in joint symptoms and psoriatic skin changes.

Web links

Individual evidence

  1. ^ Australian Public Assessment Report for Golimumab. (PDF) In: www.tga.gov.au. Australian Government, Dept. of Health & Aging, Therapeutic Goods Administration, December 2009, accessed December 21, 2010 .
  2. ↑ A Study of the Safety and Effectiveness of CNTO 148 (Golimumab) in Patients With Moderately to Severely Active Ulcerative Colitis (CR014176)
  3. ↑ Red List.
  4. ^ Website of the European Medicines Agency . Retrieved December 7, 2010.
  5. ↑ SPECIALIST INFORMATION Simponi ® 50 mg solution for injection in a pre-filled syringe (PDF; 187 kB). Retrieved November 10, 2017.
  6. ↑ Assessment report of the European Medicines Agency (PDF file; 144 kB). Retrieved December 7, 2010.
  7. ↑ EC Keystone, MC Genovese, L. Klareskog, EC Hsia, ST Hall, PC Miranda, J. Pazdur, S.-C. Bae, W. Palmer, J. Zrubek, M. Wiekowski, S. Visvanathan, Z. Wu, MU Rahman: Golimumab, a human antibody to tumor necrosis factor α given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study . In: Annals of the Rheumatic Diseases . tape 68 , no. 6 , 2009, p. 789-796 , doi : 10.1136 / ard.2008.099010 .
  8. ↑ Josef S. Smolen, Jonathan Kay, Mittie K. Doyle, Robert Landewé, Eric L. Matteson, Jürgen Wollenhaupt, Norman Gaylis, Frederick T. Murphy, Jeffrey S. Neal, Yiying Zhou, Sudha Visvanathan, Elizabeth C. Hsia, Mahboob U. Rahman: Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor [alpha] inhibitors (GO-AFTER study): a multicentre, randomized, double-blind, placebo-controlled, phase III trial . In: The Lancet . tape 374 , no. 9685 , June 18, 2009, p. 210-221 , doi : 10.1016 / S0140-6736 (09) 60506-7 .
  9. Jump up ↑ Paul Emery, Roy M. Fleischmann, Larry W. Moreland, Elizabeth C. Hsia, Ingrid Strusberg, Patrick Durez, Peter Nash, Eric Jason B. Amante, Melvin Churchill, Won Park, Bernardo Antonio Pons-Estel, Mittie K. Doyle , Sudha Visvanathan, Weichun Xu, Mahboob U. Rahman: Golimumab, a human anti-tumor necrosis factor α monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four-week results of a phase III , multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis . In: Arthritis & Rheumatism . tape 60 , no. 8 , 2009, p. 2272–2283 , doi : 10.1002 / art.24638 .
  10. ^ Robert D. Inman, John C. Davis, Désirée Van Der Heijde, Laura Diekman, Joachim Sieper, Sung Il Kim, Michael Mack, John Han, Sudha Visvanathan, Zhenhua Xu, Benjamin Hsu, Anna Beutler, Jürgen Braun: Efficacy and safety of golimumab in patients with ankylosing spondylitis: Results of a randomized, double-blind, placebo-controlled, phase III trial . In: Arthritis & Rheumatism . tape 58 , no. 11 , 2008, p. 3402–3412 , doi : 10.1002 / art.23969 .
  11. ↑ Arthur Kavanaugh, Iain McInnes, Philip Mease, Gerald G. Krueger, Dafna Gladman, Juan Gomez-Reino, Kim Papp, Julie Zrubek, Surekha Mudivarthy, Michael Mack, Sudha Visvanathan, Anna Beutler: Golimumab, a new human tumor necrosis factor α antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study . In: Arthritis & Rheumatism . tape 60 , no. 4 , 2009, p. 976–986 , doi : 10.1002 / art.24403 .