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Home > Key safety topics > Infections

Infection Rates in the MS Population

  • Patients with MS are at an increased risk of infections compared with non-MS patients1,2
  • The incidence rate of infections with monoclonal antibodies is comparable with that of the general MS population2

Overall Infections in Clinical Trials

TII-1_0
ASCLEPIOS controlled period3,a
  • During the controlled period, overall incidence of infection was similar in the ofatumumab (51.6%) and teriflunomide (52.7%) groups
    • Most common infections were upper respiratory tract and urinary tract infections
  • Herpes viral infections were reported similar in ofatumumab (4.9%) and teriflunomide (4.2%) group. All herpes viral infections were non-serious, non-disseminated, resolved with treatment, and were not opportunistic
  • Infections were mainly non-serious, Grade 1/2 severity, recovered with standard of care, and did not lead to study drug discontinuation or interruptions
Open-label extension period4,b
  • As of 30 November 2019, no increase in the overall incidence of infections was observed in the ofatumumab-treated patients (38.5%) and were consistent with the controlled period (51.6%)
IRs
IRs5yr

Serious Infections in Clinical Trials

img11
ASCLEPIOS controlled period3,a
  • Overall, the incidence of serious infections was low in the ofatumumab and teriflunomide groups (2.5% and 1.8% of patients, respectively)
Open-label extension period4,b
  • No increase in the incidence of serious infections was observed with ofatumumab (1.8% of patients)

Serious Opportunistic Infections in Clinical Trials

  • No cases of serious opportunistic infectionshave been identified during the controlled period3,a or the open-label extension period4,b
  • No cases of progressive multifocal leukoencephalopathy (PML) were reported in MS clinical studies with ofatumumab (see PML section for more details)

Serum Immunoglobulin Levels and Risk of Infections6,7

  • Treatment effect of ofatumumab on IgG and IgM levels was analyzed for over a period of 3.5 years (Data cut-off:
    29 January, 2021) in the following groups:
    • OMB overall pool (N=1969)c: Includes patients from long-term and teriflunomide/ofatumumab (TER/OMB) switch groups 
    • Long-term group (N=1292): Includes patients who received ofatumumab in the ASCLEPIOS I/II, APLIOS or APOLITOS core studies and continued with ofatumumab in the open-label extension. Patients who discontinued ofatumumab in core studies and did not enter their respective extension studies,  but continued in the safety follow-up were also included
    • TER/OMB switch group (N=677): Includes patients who received teriflunomide in the core part and switched to ofatumumab in the extension
  • Over ~3.5 years of treatment with ofatumumab, serum immunoglobulin levels were consistent with the 96-week phase 3 ASCLEPIOS trial data, which showed that
    • The mean IgG levels remained similar to baseline values and mean IgM levels remained above the LLN in the study
    • IgG levels remained similar to the baseline values in all quartiles (Q1: 8.57, Q2: 10.07 and Q3: 11.51 g/L ) while, IgM levels decreased over time in all quartiles and the mean values remained above LLN

Serum IgG & IgM levels from baseline over time

INf_Tbl_11-04
Long-term OMB, N = 1292; TER/OMB, N = 677. For all pooled analyses, a fixed value of LLN (using ALITHIOS study reference) was used: IgG: 5.65 g/L; IgM: 0.4 g/L.
Ig, immunoglobulin; LLN, lower limit of normal; SE, standard error; RMS, relapsing multiple sclerosis; TER/OMB, switched from teriflunomide to ofatumumab.

 

  • The overall incidence of serious infections in ofatumumab-treated patients was low (IR: 1.4 per 100 patient-years) for up to 3.5 years
    • One patient in the IgG levels <LLN group and
      3 patients in the IgM levels <LLN group reported serious infection
  • There was no association between decreased Ig levels and the risk of serious infections
PercentageOfPatients
n, number of patients with infections
N', total number of patients with IgG/IgM levels below LLN at least once at any time during the post-baseline visits
*Patients with ≥1 SAE infection within 1 month prior and until 1 month after any series of drop in IgM/IgG levels <LLN; LLN, lower limit of normal

Patients with ≥1 serious infection within 1 month prior and until 1 month after any series of drops in IgM/IgG <LLN

Inf_tbl_11-04
†Number of patients with IgM/IgG <LLN at least once at any time during the post-baseline visits; ‡Number of patients with no occurrence of IgM/IgG <LLN at least once at any time during the post-baseline visit; §IR per 100 PY estimated via a Poisson regression model with only treatment as the factor and with the log-link and natural logarithm of time as the offset variable. For all pooled analyses, a fixed value of LLN (using ALITHIOS study reference) was used: IgM: 0.4 g/L; IgG: 5.65 g/L
Ig, immunoglobulin; IR, incidence rate; LLN, lower limit of normal; PT, preferred term; PY, patient-year.
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Additional information

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aIncludes data of patients pooled from the ASCLEPIOS I and ASCLEPIOS II trials during the controlled treatment period.

bOpen-label extension includes cumulative data of all patients (N=1873) who were randomized to ofatumumab 20 mg in ASCLEPIOS I, ASCLEPIOS II, APLIOS studies, completed the core period of the study, and continued to be treated with ofatumumab 20 mg in open-label ALITHIOS or either completed or discontinued the core period of the study and continued with safety follow-up epoch of the core study and newly switched group (who were randomized to teriflunomide 14 mg in ASCLEPIOS I and ASCLEPIOS II, completed the core period of the study, and switched to ofatumumab 20 mg in open-label ALITHIOS).

cIncludes cumulative data of all patients (N=1969) who were randomized to ofatumumab 20 mg in ASCLEPIOS I, ASCLEPIOS II, APLIOS studies, completed the core period of the study, and continued to be treated with ofatumumab 20 mg in open-label ALITHIOS or either completed or discontinued the core period of the study and continued with safety follow-up epoch of the core study and newly switched group (who were randomized to teriflunomide 14 mg in ASCLEPIOS I and ASCLEPIOS II, completed the core period of the study, and switched to ofatumumab 20 mg in open-label ALITHIOS).
References
1. Jick S, et al. Presented at ACTRIMS 2020 Forum. P086.
2. Persson R, et al. Mult Scler Relat Disord. 2020;41:101982.
3. Data on file. OMB157 Summary of clinical safety in RMS. Novartis Pharma AG; 2020.
4. Hauser SL et al., Mult Scler. 2022. doi: 10.1177/13524585221079731.
5. Data on file. OMB 157 T054a Table L2 5.1, 5.9. (Data cut off: 29 Jan 2021). Novartis Pharma AG.
6. Jasińska E, et al. Presented at EAN 2021. OPR-207.
7. Wiendl  H, et al. Presented at ECTRIMS 2021.