Table 2. Summary of AEs by Treatment Sequence and ADA/NAb Results to Week 48a.
| Safety population | No. (%) | ||
|---|---|---|---|
| Biosim-NTZ (n = 131) | Ref-NTZ/biosim-NTZ switch (n = 30) | Ref-NTZ (n = 103) | |
| Any TEAE | 85 (64.9) | 22 (73.3) | 71 (68.9) |
| Any related TEAE | 31 (23.7) | 8 (26.7) | 22 (21.4) |
| Any TEAE ≥grade 3 | 4 (3.1) | 0 | 1 (1.0) |
| Investigations | 2 (1.5) | 0 | 0 |
| Musculoskeletal and connective tissue disorders | 0 | 0 | 1 (1.0) |
| Respiratory, thoracic, and mediastinal disorders | 1 (0.8) | 0 | 0 |
| Skin and subcutaneous tissue disorders | 1 (0.8) | 0 | 0 |
| Any TEAE of special interest | 6 (4.6) | 2 (6.7) | 6 (5.8) |
| Immune system disorders | 0 | 1 (3.3) | 0 |
| Infections and infestations | 2 (1.5) | 1 (3.3) | 5 (4.9) |
| Investigations | 1 (0.8) | 0 | 0 |
| Skin and subcutaneous tissue disorders | 3 (2.3) | 0 | 1 (1.0) |
| Any TEAE leading to permanent study drug discontinuation | 8 (6.1)b | 1 (3.3)c | 3 (2.9)d |
| Any TEAE leading to withdrawal from studye | 0 | 0 | 0 |
| ADA prevalence at baseline | 9 (7) | 1 (3) | 7 (7) |
| Treatment-emergent ADA positivity, total incidence | 104 (79) | 23 (77) | 76 (74) |
| Neutralizing ADA (NAb) | 90 (69) | 20 (67) | 69 (67) |
| % of ADA positive | 87 | 87 | 91 |
Abbreviations: ADA, antidrug antibody; AE, adverse event; biosim-NTZ, biosimilar natalizumab; NAb, neutralizing antibody; ref-NTZ, reference natalizumab; TEAE, treatment-emergent adverse event.
The number and percentage of patients with TEAEs, AEs of special interest (ie, progressive multifocal leukoencephalopathy, John Cunningham virus granule cell neuronopathy, opportunistic infections, liver injury, hypersensitivity, encephalitis, meningitis, and acute retinal necrosis), and serious AEs that occurred after the start of the first infusion and through 4 weeks after the last infusion date of the study drug (visit 13, end of study visit), were summarized by MedDRA system organ class and preferred term overall, by severity, and by relationship to study drug for each treatment group.
Urticaria (n = 2); pruritus (n = 2); asthenia, hyperhidrosis, blood pressure fluctuations, and dizziness (n = 1); trigeminal neuralgia, herpes simplex, and ear infection (n = 1); COVID-19 (n = 1); hypotension (n = 1).
Hypersensitivity (n = 1).
Urinary tract infection (n = 1); pharyngitis (n = 1); urticaria and angioedema (n = 1).
A TEAE was considered to lead to withdrawal from the study only if the patient did not proceed to progressive multifocal leukoencephalopathy follow-up because of this event.