If a patient on weekly subcutaneous Humira (adalimumab) switches to the biosimilar adalimumab‑ADBM, does that increase their risk of diffuse large B‑cell lymphoma?

Switching to Adalimumab Biosimilar Does Not Increase DLBCL Risk

Switching from weekly subcutaneous Humira (adalimumab) to the biosimilar adalimumab-ADBM does not increase the risk of diffuse large B-cell lymphoma beyond the baseline class-related risk inherent to all TNF-α inhibitors. 1

Understanding the Lymphoma Risk with TNF-α Inhibitors

The risk of lymphoma, including DLBCL, is a class effect of all TNF-α antagonists—not specific to any particular formulation or brand. 1 This means:

• All TNF-α inhibitors carry an inherent lymphoma risk due to their mechanism of action (TNF-α blockade), regardless of whether they are reference products or biosimilars. 1
• The standardized incidence ratio for lymphomas with adalimumab in rheumatoid arthritis was reported as 2.98 (95% CI 1.89–4.47) in clinical trials. 2
• A French national registry (RATIO) found the overall sex and age-adjusted incidence rate of lymphoma was 42.1 per 100,000 patient-years with anti-TNF therapy, with a standardized incidence ratio of 2.4 (95% CI 1.7–3.2). 3
• This two- to threefold increased risk is similar to what is expected in patients with severe inflammatory diseases themselves, independent of biologic therapy. 3

Safety of Biosimilar Switching

Multiple high-quality guideline documents confirm that switching from reference adalimumab to any approved biosimilar yields comparable safety profiles with no new safety signals. 1 The evidence is robust:

• Clinical studies of switches to biosimilars (including SB5, GP2017, MSB11022, and others) have demonstrated similar overall adverse-event rates and no increase in serious adverse events or malignancies compared with continued reference-product use. 1
• A systematic review of 22 studies covering ≥10 different adalimumab biosimilars across various therapeutic indications showed that immunogenicity and safety outcomes did not change quantitatively or qualitatively after switching. 1
• Real-world data from European countries where adalimumab biosimilars have been marketed since 2017 report no adverse safety events specifically linked to biosimilar switching. 1
• The 2020 EULAR systematic literature review on biosimilar DMARDs found no difference in safety or efficacy when switching from reference adalimumab to biosimilars. 2

Critical Clinical Interpretation

The lymphoma risk is attributable to exposure to TNF-α inhibitors as a drug class, not to the act of switching between adalimumab formulations. 1 This distinction is crucial:

• Biosimilar adalimumab-ADBM has demonstrated bioequivalence and comparable safety to the reference product, supporting its use as a direct substitute. 1
• No evidence indicates that switching from weekly Humira to adalimumab-ADBM raises lymphoma risk beyond the baseline class effect. 1
• If a patient develops lymphoma while receiving any TNF-α inhibitor, this should be interpreted as a known class-related risk rather than a consequence of product switching. 1
• Temporal association does not imply causation—clinicians should avoid attributing lymphoma development to the switching process alone. 1

Monitoring and Pharmacovigilance

Standard monitoring protocols for biosimilars should be identical to those for reference products; no separate or additional surveillance is required. 1 However:

• Robust pharmacovigilance systems are mandated for all biologics, including biosimilars, to enable detection of rare safety events. 1
• Accurate documentation of the specific biologic product used is essential when switching to ensure reliable adverse-event reporting. 1
• Standard monitoring for patients on TNF-α inhibitors should continue unchanged, encompassing routine infection surveillance, malignancy screening, and annual safety-efficacy review. 1

Common Pitfalls to Avoid

• Do not attribute increased lymphoma risk to biosimilar switching—the risk is inherent to the TNF-α inhibitor class and exists equally with reference products. 1
• Avoid unnecessary anxiety about biosimilar switches—stringent regulatory approval ensures biosimilarity in efficacy, safety, and immunogenicity. 1
• Do not implement additional monitoring protocols for biosimilars beyond what is standard for reference adalimumab. 1
• Recognize that some lymphomas may be EBV-associated and related to immunosuppression rather than the specific drug. 2, 3

Additional Context on Adalimumab-Associated Lymphoma

While not specific to biosimilars, clinicians should be aware of the broader lymphoma risk profile:

• Rare cases of primary CNS lymphoma have been reported with adalimumab, though this remains extremely uncommon. 4
• The French RATIO registry found higher lymphoma risk with monoclonal antibodies (adalimumab, infliximab) compared to etanercept: SIR 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4–1.8), respectively. 3
• Epstein-Barr virus was detected in some lymphoma cases associated with anti-TNF therapy, suggesting an immunosuppression-related mechanism. 3

In summary, switching to adalimumab-ADBM biosimilar does not increase DLBCL risk—the lymphoma risk is a class effect of TNF-α inhibition that persists regardless of which specific adalimumab product is used. 1