Exploring the evolution of understanding around infection risks with Novartis' MS therapy Kesimpta
Imagine your immune system as a highly trained security team that suddenly turns against your own headquarters—your brain and spinal cord. This is the reality of multiple sclerosis (MS), where the body's defenses mistakenly attack the protective covering of nerve fibers.
For decades, treating MS has meant walking a therapeutic tightrope: suppressing enough of this rogue immune activity to prevent disability, while leaving the body with sufficient defenses to fight real threats like viruses and bacteria. In 2008, a cloud of concern formed when early research into a new class of MS therapies highlighted potential infection risks 2 . But does this cloud still linger today? The story of how one medication—Novartis' Kesimpta (ofatumumab)—navigated these concerns reveals a fascinating evolution in our understanding of MS treatment safety.
MS treatment requires balancing immune suppression for efficacy with preservation of infection-fighting capability—a challenge that has evolved significantly with newer therapies.
MS was long considered primarily a T-cell mediated disease, but research breakthroughs revealed that B-cells play a surprisingly central role in the condition's development 5 . These immune cells don't just produce antibodies; they also activate harmful T-cells and create inflammation that damages the nervous system.
Anti-CD20 therapies like Kesimpta work by targeting a specific protein—CD20—found on the surface of mature B-cells. By binding to this protein, these treatments effectively deplete the problematic B-cells driving the MS disease process. What makes this approach particularly innovative is its selectivity: it primarily affects mature B-cells while largely sparing other immune components, including the antibody-producing plasma cells and early B-cell precursors 5 . This selective targeting theoretically offers a safety advantage over broader immunosuppressants.
The infection concern with any immune-modulating therapy stems from a simple principle: if you suppress parts of the immune system, you might reduce its ability to fight genuine threats. This concern became particularly prominent during the COVID-19 pandemic, when researchers closely examined whether certain MS treatments left patients more vulnerable to severe outcomes 6 .
The scientific community needed to answer critical questions: Would reducing B-cell levels compromise vaccine responses? Would patients face higher rates of serious infections requiring hospitalization? The answers to these questions would determine whether the benefits of treatment outweighed the potential risks for people living with MS.
Initial research identifies B-cells as more than just antibody producers in MS pathology 5 .
Concerns raised about potential infection risks with new class of MS therapies 2 .
Anti-CD20 therapies developed with selective B-cell targeting approach.
To address these crucial safety questions, Novartis initiated the ALITHIOS study, an ongoing open-label extension trial designed to evaluate the long-term safety and effectiveness of Kesimpta in people with relapsing forms of MS 8 . This study isn't a brief snapshot—it follows patients for years, with some participants now having over seven years of continuous data 7 .
The study includes patients who completed earlier Kesimpta trials, creating a substantial pool of over 1,900 participants who have received at least one dose of the medication 4 . This large sample size provides the statistical power needed to detect even uncommon side effects.
The data collected from ALITHIOS and other studies presents a comprehensive picture of Kesimpta's safety profile. The findings have been consistent enough to convince regulatory agencies worldwide—Kesimpta has now been approved in over 92 countries with more than 150,000 patients treated as of August 2025 1 .
Countries Approved
Patients Treated
Years of Data
Study Participants
| Safety Metric | Rate per 100 Patient-Years | Interpretation |
|---|---|---|
| Any Adverse Events | 124.65 | Consistent with expected background rates |
| Serious Adverse Events | 4.68 | No increase over time observed |
| Serious Infections | 1.63 | Remained low and stable |
| Malignancies | 0.32 | No increased risk detected |
Over five years of continuous treatment, the exposure-adjusted incidence rates of serious infections remained low at 1.63 per 100 patient-years, with no increase observed over time 4 . This consistency suggests that the immune system maintains its ability to fight serious infections despite B-cell depletion.
The COVID-19 pandemic provided an unexpected but crucial real-world test for all immunomodulating therapies. Researchers tracked how Kesimpta-treated patients fared throughout the pandemic, with revealing results.
| Outcome Measure | Result | Context |
|---|---|---|
| Total COVID-19 Cases | 14.3% of patients | Most mild/moderate (90.6%) |
| Hospitalization Rate | 9.4% | Lower than general MS population (15.5-21.5%) |
| Fatal Outcomes | 0.8% | Lower than general MS population (1.97%) |
| Vaccine Breakthrough | 1.5% | Comparable to general population |
| Recovery Rate | 98.4% | Majority recovered without complication |
Perhaps most reassuringly, when vaccinated patients did contract COVID-19, the outcomes were generally positive. The rate of breakthrough infections in fully vaccinated patients (1.5%) aligned with the rate reported in the fully vaccinated general population during the same period 8 .
| Therapy Class | Example Medications | Severe Infection Risk | Notes |
|---|---|---|---|
| Anti-CD20 | Kesimpta, ocrelizumab |
|
Preserved immunoglobulin levels |
| Fumarates | Dimethyl fumarate |
|
Linked to more severe infections |
| S1P Modulators | Fingolimod |
|
|
| Relocation Agents | Natalizumab |
|
A real-world study comparing infection risks across different MS therapies found that patients on fumarates had higher rates of severe infections, while natalizumab and anti-CD20 therapies like Kesimpta appeared safer over extended use 6 . This suggests that the infection risk profile varies significantly across MS treatments, with Kesimpta positioned favorably within the treatment landscape.
One of the most important findings helping to explain Kesimpta's favorable infection profile involves its effect on immunoglobulins—the proteins crucial for fighting infections. Unlike some broader immunosuppressants, Kesimpta preserves baseline levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) over time 9 .
This preservation occurred even with prolonged treatment up to 3.5 years, and critically, no association was found between decreased immunoglobulin levels and the risk of infections 9 . This helps explain why patients can experience significant clinical benefits from B-cell depletion without necessarily facing increased infection risks.
Illustration showing preserved IgG and IgM levels over extended treatment periods 9
The accumulating evidence has significant implications for how neurologists and patients approach MS treatment decisions. The data presented at major medical conferences in 2025—including seven-year disability outcomes showing more than 90% of patients receiving first-line Kesimpta were progression-free for up to seven years—reinforces the medication's favorable benefit-risk profile 1 7 .
This long-term safety record supports the growing trend toward early intervention with high-efficacy therapies in MS. As research increasingly shows that early treatment initiation leads to better long-term outcomes, having safe, effective first-line options becomes crucial 4 .
| Research Component | Function in MS Therapy Development |
|---|---|
| Anti-CD20 Monoclonal Antibodies | Target and deplete specific B-cells involved in MS pathology |
| Magnetic Resonance Imaging (MRI) | Measures new/enlarging T2 lesions and gadolinium-enhancing lesions as markers of disease activity |
| Immunoglobulin Level Monitoring | Tracks IgG/IgM levels to assess infection-fighting capacity during treatment |
| Serum Neurofilament Light Chain (sNfL) | Serves as a biomarker of nerve cell damage, measuring treatment effectiveness |
| Extended Disability Status Scale (EDSS) | Quantifies disability progression and improvement in clinical trials |
| Vaccination Response Studies | Assesses how well the immune system responds to vaccines while on treatment |
Tools like the EDSS provide standardized measures of disability progression, allowing researchers to quantify treatment effectiveness across studies and patient populations.
Biomarkers like serum neurofilament light chain offer objective measures of nerve damage, complementing clinical assessments and imaging findings.
The journey of Kesimpta—from initial theoretical concerns about infection risk to a well-established safety profile supported by years of data—illustrates how rigorous long-term research can transform medical understanding.
What began as a "cloud" over MS therapy has evolved into a nuanced appreciation of how selective B-cell depletion can effectively control MS while maintaining the immune system's crucial protective functions.
The ALITHIOS study and other research efforts have demonstrated that the infection risk with Kesimpta remains low and stable over time, with preserved immunoglobulin levels helping to maintain infection-fighting capability 4 9 .
This favorable safety profile, combined with sustained efficacy, positions Kesimpta as a treatment option that enables people with MS to aggressively manage their disease without undue concern about infection complications.
For the nearly 3 million people living with MS worldwide 1 , this evolving understanding represents more than just scientific progress—it represents hope for a life where disease activity can be controlled without constant worry about the treatment itself. As research continues, the MS community can look forward to even more refined therapies that further narrow the gap between efficacy and safety.
Long-term data from the ALITHIOS study demonstrates that Kesimpta maintains a favorable safety profile with low, stable infection rates over extended treatment periods, supporting its use as a first-line therapy for relapsing MS.