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KESIMPTA®▼ (ofatumumab) is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis with active disease defined by clinical or imaging features.
For full safety information, please refer to the GB KESIMPTA Summary of Product Characteristics (SmPC) and NI KESIMPTA Summary of Product Characteristics (SmPC).
KESIMPTA was generally well tolerated, with 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.1,2,4
On this page, you can find data for specific adverse events with KESIMPTA versus teriflunomide, such as infection rates and injection-site reactions, treatment discontinuations and immunoglobulin data. View the links below to learn more about specific data.
In ASCLEPIOS I (n=927) and II (n=955):
KESIMPTA resulted in similar infection rates to teriflunomide1,2
Injection-related reactions were mostly (99.8%) mild-to-moderate in severity1,2
Incidence of systemic injection-related reactions fell with each injection:1,2
- 14.4% with the first
- 4.4% with the second
- <3% from the third
Two (0.2%) patients in the KESIMPTA arm reported serious injection-related reactions
No incidences of injection-related reactions were life threatening1,2
Treatment discontinuations:1–3
In the ongoing Phase IIIb ALITHIOS study, 1703 RMS patients were treated with KESIMPTA as of data cut-off (September 2021)3,5
ALITHIOS safety results
ALITHIOS is an open-label, single-arm, umbrella extension, Phase IIIb trial designed to assess the benefit-risk profile of KESIMPTA (20 mg SC every 4 weeks) and its tolerability for up to 5 years in RMS patients (N=1703).3,5
The primary outcome measure for the study is the number of patients who experience an adverse event or abnormal laboratory, vital and/or ECG result and positive suicidality outcomes.5
Click here for more details about ALITHIOS study design and other clinical trial designs
In ALITHIOS:
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Mean IgG levels remained stable in KESIMPTA-treated patients for up to 5 years3
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A decrease in mean IgM levels was observed for KESIMPTA-treated patients, but remained above the LLN for up to 5 years†3
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Over 5 years, Ig levels remained above the LLN in the majority of patients3
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The overall rate of AEs and severe AEs remained consistent with ASCLEPIOS3
Adverse reactions as per the SmPC‡1,2
Adverse events recorded in ASCLEPIOS, n (%)4,6
Please refer to the Summary of Product Characteristics for full information.1,2
Considerations before starting
Prescribing considerations and precautions: before treatment initiation1,2
Contraindications
- Hypersensitivity to the active substance or to any of the excipients in KESIMPTA
- Patients in a severely immunocompromised state
- Severe active infection until resolution
- Known active malignancy
Treatment of severely immunocompromised patients
- It is not recommended to use other immunosuppressants concomitantly with KESIMPTA except corticosteroids for symptomatic treatment of relapses
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 at least 2 weeks prior to initiation of KESIMPTA
Pregnancy and family planning
- Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving KESIMPTA and for 6 months after the last administration of KESIMPTA, as there is a limited amount of data from the use of KESIMPTA in pregnant women. Treatment with KESIMPTA should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus
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. 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)
Hepatitis B virus (HBV) reactivation
- HBV screening should be performed in all patients before initiation of treatment with KESIMPTA
- HBV reactivation has occurred in patients treated with anti-CD20 antibodies, patients with active HBV infection should not be treated with KESIMPTA
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
- The first injection should be performed under the guidance of an appropriately trained HCP
Considerations after starting
Prescribing considerations and precautions: after treatment initiation1,2
HBV reactivation
- HBV reactivation has occurred in patients treated with anti-CD20 antibodies, patients with active HBV infection should not be treated with KESIMPTA
Injection-related reactions
- 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
Infections
- Based on its mode of action and available clinical experience, KESIMPTA has the potential for an increased risk of infections. Administration should be delayed in patients with an active infection until the infection is resolved
- 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
Vaccinations
- The safety of immunisation with live or live-attenuated vaccines following KESIMPTA therapy has not been studied. Vaccination with live or live-attenuated vaccines is not recommended during treatment and after discontinuation until B-cell repletion
Vaccination of infants born to mothers treated with KESIMPTA during pregnancy
- In infants of mothers treated with KESIMPTA 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
Lactation
- The use of KESIMPTA in women during lactation has not been studied. It is unknown whether KESIMPTA is excreted in human milk. In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, which decreases to low concentrations soon afterwards. Consequently, a risk to the breast-fed child cannot be excluded during this short period. Afterwards, KESIMPTA could be used during breastfeeding if clinically needed. However, if the patient was treated with KESIMPTA up to the last few months of pregnancy, breastfeeding can be started immediately after birth
Mean lymphocyte levels (after Week 4) and mean neutrophil levels remained stable throughout 4 years of treatment with KESIMPTA7
Lymphocyte levels7
Adapted from Saccà F, et al. 2022.
Neutrophil levels7
Adapted from Saccà F, et al. 2022.
No apparent association was observed between low lymphocyte or low neutrophil levels and risk of serious infection***6
98.4% of KESIMPTA-treated patients recovered from COVID-19¶¶8
Lymphocyte levels
There was no evidence of increased risk of severe COVID-19 or fatal outcomes in KESIMPTA patients, compared with the general and MS populations8–10
Learn more about COVID-19 outcomes in the ALITHIOS study by watching a summary presentation by consultant neurologist Dr David Paling.
Refer to SmPC for full prescribing information.
*Teriflunomide group received placebo injections.1,2
†ALITHIOS includes patients who either continued on KESIMPTA treatment from the Phase III ASCLEPIOS trials or the Phase II APLIOS and APOLITOS trials or switched from teriflunomide in the ASCLEPIOS trials to KESIMPTA.3,5
‡Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
§Grouping of preferred terms (PTs) was considered for 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.1,2
¶Grouping of preferred terms (PTs) was considered for ADR frequency determination and includes the following: urinary tract infection, cystitis, Escherichia urinary tract infection, asymptomatic bacteriuria, bacteriuria.1,2
‖Patients in the teriflunomide arm received matching placebo to ensure blinding (double-dummy design).
**Systemic: relating to or affecting the body as a whole, rather than individual parts and organs.11 In ASCLEPIOS, systemic reactions were those that occurred within 24 hours after the injection. Symptoms observed included fever, headache, myalgia, chills and fatigue and were predominantly (99.8%) non-serious and mild-to-moderate in severity.
††Local: limited to a particular part of the body.11 In ASCLEPIOS, local site IRRs could be reported without any time limit from the time the injection was administered. All IRRs (local) were mild-to-moderate in severity and non-serious. IRR (local) symptoms observed in clinical studies included erythema, swelling, itching and pain.
‡‡Switching period refers to the patients started with teriflunomide and not applicable to the patients with KESIMPTA in core period; for teriflunomide/KESIMPTA group, data from 1st dose of teriflunomide until last dose of KESIMPTA plus 100 days/analyses cut-off date have been used; R1: the first patient with first treatment emergent assessment in KESIMPTA period after switching to KESIMPTA (72 weeks); R2: the last patient with last treatment emergent assessment in teriflunomide period before switching to KESIMPTA (120 weeks).7
§§Exposure-adjusted incidence rate of lymphopenia and neutropenia remained low (0.31 [95% CI: 0.19, 0.51]).7
¶¶Recovered includes recovered or recovered with sequelae or recovering at the time of data cut-off.8
‖‖Severity was graded by CTCAE v5.0 as assessed by investigators.8
***Breakthrough infection classed as confirmed COVID-19 after being fully vaccinated.8
ADR, adverse drug reaction; AE, adverse event; CD, cluster of differentiation; CI, confidence interval; COVID-19, coronavirus disease 2019; CTCAE, The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE [v5.0]); ECG, electrocardiogram; HBV, hepatitis B virus; HCP, healthcare professional; IgG, immunoglobulin G; IgM, immunoglobulin M; IRR, injection-related reaction; LLN, lower limit of normal; MoA, mode of action; MRI, magnetic resonance imaging; MS, multiple sclerosis; NA, not applicable; PML, progressive multifocal leukoencephalopathy; R, randomisation; RMS, relapsing forms of multiple sclerosis; RT-PCR, reverse transcriptase polymerase chain reaction; SC, subcutaneous; SE, standard error.
References
- KESIMPTA (ofatumumab) Summary of Product Characteristics, Great Britain; July 2022.
- KESIMPTA (ofatumumab) Summary of Product Characteristics, Northern Ireland; July 2022.
- Cohen JA, et al. Poster P8.004 presented at the American Academy of Neurology (AAN). April 2023.
- Hauser SL, et al. New Engl J Med 2020;383:547–547, and supplementary material.
- Clinicaltrials.gov. NCT03650114. Available at: https://clinicaltrials.gov/ct2/show/NCT03650114 [Accessed December 2022].
- Hauser SL, et al. Oral presentation 336 presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 2019; Stockholm, Sweden.
- Saccà F, et al. Oral presentation OPR134 presented at the European Academy of Neurology (EAN). June 2022.
- Cross AH, et al. Neurol Ther 2022;11:741–758 and supplementary material.
- Prosperini L, et al. J Neurol 2022;269(3):1114–1120.
- Barzegar M, et al. Neurol Neuroimmunol Neuroinflamm 2021;8(4):e1001.
- Cambridge Dictionary. Local [online]. Available at: https://dictionary.cambridge.org/dictionary/english/local [Accessed December 2022].
