Prescribing information

 

   

KESIMPTA demonstrated a safety and tolerability profile similar to teriflunomide in clinical trials1–3

The safety profile of KESIMPTA compared with teriflunomide was characterised in the ASCLEPIOS I and II studies.1–3

For full safety information, please refer to the KESIMPTA Summary of Product Characteristics (SmPC) by clicking here for GB and here for NI. 

Similar infection rates to teriflunomide.1,2

 

Similar discontinuation rates between the two treatment groups (KESIMPTA:
5.7% vs teriflunomide: 5.2%).1–3

 

Injection-related reactions were mostly (99.8%) mild-to-moderate in severity.
Two (0.2%) patients in the KESIMPTA arm reported serious injection-related
reactions. No incidences of injection-related reactions were life threatening.1,2

 

ASCLEPIOS adverse events (AEs), n (%)3,4

SmPC table of adverse reactions1,2

Infections and infestations
Very common Upper respiratory tract infection

Urinary tract infections§
Common Oral herpes
General disorders and administration site conditions
Very common Injection-site reactions (local)
Injury, poisoning and procedural complications
Very common Injection-related reactions (systemic)
Investigations
Common Blood immunoglobulin M decreased

Any changes in IgM were not correlated with infection rates1,2,5

Average IgG and IgM levels remained within reference range in clinical trials||1,2,5

At 120 weeks:

KESIMPTA was associated with a transient decrease of 4.3% in mean IgG levels after 48 weeks, with an increase of 2.2% after 96 weeks.#1,2,5

 

In 14.3% of patients in the relapsing forms of MS (RMS) Phase III clinical studies, treatment with KESIMPTA resulted in a decrease in IgM that reached a value below 0.34 g/dL.#1,2

 

KESIMPTA contraindications1,2

  • Hypersensitivity to the active substance or to any of the excipients listed in the SmPC
  • Patients in a severely immunocompromised state
  • Severe active infection until resolution
  • Known active malignancy

Prescribing considerations and precautions1,2

Hepatitis B virus (HBV) reactivation

  • HBV reactivation has occurred in patients treated with anti-CD20 antibodies, patients with active HBV infection should not be treated with KESIMPTA
  • HBV screening should be performed in all patients before initiation of treatment with KESIMPTA 
 

Vaccinations

  • Vaccination with live or live-attenuated vaccines is not recommended during treatment with KESIMPTA, all live or live-attenuated vaccines should be administered at least 4 weeks prior to start of treatment
  • KESIMPTA may interfere with the effectiveness of inactivated vaccines. Inactivated vaccines, whenever possible, should be administered 2 weeks prior to initiation of KESIMPTA
 

Vaccination of infants born to mothers treated with KESIMPTA during pregnancy

  • In infants of mothers treated with ofatumumab during pregnancy, live or live-attenuated vaccines should not be administered before the recovery of B-cell counts has been confirmed. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines 
  • Inactivated vaccines may be administered as indicated prior to recovery from B-cell depletion; however, assessment of vaccine immune responses, including consultation with a qualified specialist, should be considered to determine whether a protective immune response was mounted
 

Pregnancy and family planning

  • Women of childbearing potential should use effective contraception while receiving KESIMPTA, as there is a limited amount of data from the use of KESIMPTA in pregnant women 
  • Patients should continue using contraception to avoid pregnancy for 6 months following their last dose of KESIMPTA
 

Infections

  • It is recommended to evaluate the patient’s immune status prior to initiating therapy
  • Based on its mode of action and available clinical experience, KESIMPTA has the potential for an increased risk of infections. Therefore, administration should be delayed in patients with an active infection until the infection is resolved
  • KESIMPTA must not be given to patients in a severely immunocompromised state (e.g. significant neutropenia or lymphopenia)
  • John Cunningham virus (JCV): Physicians should be vigilant for medical history of progressive multifocal leukoencephalopathy (PML) and for any clinical symptoms or MRI findings that may be suggestive of PML. If PML is suspected, treatment with KESIMPTA should be suspended until PML has been excluded 
 

Treatment of severely immunocompromised patients

  • Patients in a severely immunocompromised state must not be treated until the condition resolves
  • It is not recommended to use other immunosuppressants concomitantly with KESIMPTA except corticosteroids for symptomatic treatment of relapses
 

Injection-related reactions

  • Patients should be informed that injection-related reactions (systemic) could occur, generally within 24 hours and predominantly following the first injection. Only limited benefit of premedication with steroids was seen in RMS clinical studies
  • Injection-related reactions can be managed with symptomatic treatment, should they occur. Therefore, use of premedication is not required
  • Injection site reaction (local) symptoms observed in clinical studies included erythema, swelling, itching and pain
  • The first injection should be performed under the guidance of an appropriately trained healthcare professional
 

AE=adverse event; HBV=hepatitis B virus; Ig=immunoglobulin; JCV=john cunningham virus; MRI=magnetic resonance imaging; PML=progressive multifocal leukoencephalopathy; RMS=relapsing forms of multiple sclerosis; SmPC=summary of product characteristics.

*Symptoms observed included fever, headache, myalgia, chills and fatigue and were predominantly (99.8%) non-serious and mild-to-moderate in severity.
Injection site reaction (local) symptoms observed in clinical studies included erythema, swelling, itching and pain. All injection-site reactions (local) were mild-to-moderate in severity and non-serious.
Grouping of preferred terms (PTs) was considered for adverse drug reaction (ADR) frequency determination and includes the following: nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, rhinitis, viral upper respiratory infection, tonsillitis, acute sinusitis, pharyngotonsillitis, laryngitis, pharyngitis streptococcal, viral rhinitis, sinusitis bacterial, tonsillitis bacterial, viral pharyngitis, viral tonsillitis, chronic sinusitis, nasal herpes, tracheitis.
§Grouping of PTs was considered for ADR frequency determination and includes the following: urinary tract infection, cystitis, Escherichia urinary tract infection, asymptomatic bacteriuria, bacteriuria.
#Serum IgG/IgM levels were monitored at baseline, Weeks 4 and 12 and every 12 weeks thereafter (KESIMPTA, n = 946; teriflunomide, n = 936).5
||Average IgG levels remained well within the reference ranges (patients aged 16-19 years: 5.49-15.84 g/L; patients aged >19 years: 7.00-16.00 g/L).Average IgM levels remained well within the reference ranges (patients aged 16-19 years: 0.23-2.59 g/L; patients aged >19 years: 0.40-2.30 g/L)

References

  1. KESIMPTA [Summary of Product Characteristics]. Great Britain: Novartis Pharmaceuticals UK Ltd; April 2021.
  2. KESIMPTA [Summary of Product Characteristics]. Novartis Ireland Limited; March 2021.
  3. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. New Engl J Med. 2020;383:547–547.
  4. Hauser SL, Bar-Or A, Cohen J, et al. Efficacy and safety of ofatumumab versus teriflunomide in RMS: Phase 3 ASCLEPIOS I and II trials. Presented at: 25th ECTRIMS Congress; September 2019; Stockholm, Sweden.
  5. de Seze J, Bar-Or A, Correale J, et al. Serum immunoglobulin levels and infection risk in the Phase 3 trials of ofatumumab in relapsing multiple sclerosis [Poster P0236]. Presented at: 8th Joint ACTRIMS-ECTRIMS Meeting, MS Virtual 2020; 11–13 September 2020.
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UK | June 2021 | 132032
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
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