Management of Low IgM on Kesimpta (Ofatumumab)
Monitor IgM levels regularly and continue Kesimpta while implementing infection surveillance, but consider immunoglobulin replacement therapy if the patient develops recurrent severe infections (≥2 episodes with encapsulated bacteria) regardless of the absolute IgM level. 1, 2
Immediate Monitoring Strategy
Check immunoglobulin levels (IgG, IgM, IgA) at baseline, during treatment, and after discontinuation until B-cell repletion occurs. 2 The FDA label for Kesimpta explicitly requires this monitoring due to the known risk of immunoglobulin reduction.
Monitor monthly if immunoglobulin replacement therapy is initiated. 1 This frequency allows for dose adjustments based on trough levels and clinical response.
Track infection frequency and severity more closely than absolute immunoglobulin numbers. 3 Serum levels alone do not adequately reflect an individual's capacity to mount antibody responses against pathogens.
Clinical Significance of Low IgM
Low IgM increases infection risk, particularly with encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae). 1 This is the primary clinical concern driving management decisions.
IgM hypogammaglobulinemia was the most common cause of Kesimpta discontinuation in clinical trials (3.3% of patients). 2 However, discontinuation should not be automatic based solely on laboratory values.
In clinical trials, 14.3% of Kesimpta-treated patients developed IgM below 0.34 g/L, but this was not associated with increased infection risk in the trial population. 2 Real-world experience may differ, particularly with longer treatment duration.
Treatment Thresholds for Immunoglobulin Replacement
Consider IVIG or SCIG replacement therapy in the following scenarios: 3, 1
- Patients with ≥2 severe recurrent infections by encapsulated bacteria, regardless of IgG or IgM level (strongest indication)
- Patients with IgG <400 mg/dL (even if IgM is the primary abnormality, check IgG levels)
- Patients with life-threatening infections
- Patients with documented bacterial infection showing insufficient response to antibiotic therapy
Dosing Protocol for Immunoglobulin Replacement
Initiate IVIG at 0.4 g/kg body weight every 3-4 weeks 4 or SCIG at equivalent doses administered weekly or biweekly. 4
Target trough IgG level of 600-800 mg/dL (or >500-700 mg/dL per alternative guidelines). 4 While the primary abnormality is IgM, IgG replacement provides broader protection against encapsulated bacteria.
Continue monthly IVIG for the duration of immunoparesis until immunoglobulin levels recover. 3, 1
Kesimpta Continuation Decision
Maintain Kesimpta dosing during immunoglobulin replacement therapy. 3, 1 The FDA label and expert consensus support continuing the disease-modifying therapy while managing the immunological complication.
Consider discontinuing Kesimpta only if: 2
- The patient develops a serious opportunistic infection
- Recurrent infections occur despite immunoglobulin replacement
- Immunoglobulin levels indicate severe immune compromise with clinical consequences
Infection Prevention Strategies
Avoid live-attenuated or live vaccines during Kesimpta treatment and after discontinuation until B-cell repletion. 2 This is an FDA-mandated precaution.
Delay Kesimpta administration if an active infection is present until the infection resolves. 2
Educate patients on early signs of infection (fever, respiratory symptoms, urinary symptoms) and establish a low threshold for seeking medical attention. 5
Consider prophylactic antibiotics in select high-risk patients with recurrent infections, though this is not routinely recommended for isolated low IgM. 3
Interpretation Pitfalls
IgG and IgM serology tests for viral infections should be interpreted with caution in patients on Kesimpta, as they may have false-negative results due to failure to mount antibody responses. 3, 1
If the patient has received IVIG, serological test results may be confounded by passively transferred antibodies. 3
Do not assume all hypogammaglobulinemia requires replacement therapy—verify infection history and clinical impact before initiating costly immunoglobulin therapy. 4
Real-World Evidence Considerations
Recent observational data show that 87% of patients on anti-CD20 therapy (ocrelizumab) with IgG in the lower normal range had sub-protective antibody responses to pneumococcus/Haemophilus influenzae, 5 suggesting that even "normal" immunoglobulin levels may not guarantee adequate protection. This reinforces the importance of monitoring infection frequency rather than relying solely on laboratory values.
One case report documented successful continuation of ofatumumab despite selective IgM deficiency with close monitoring and no infectious complications, 6 supporting the strategy of continuing therapy with enhanced surveillance in selected patients.