Patient enrolment and disposition
| Number of patients enrolled in TOP | 4821 |
|---|---|
| Enrolment by number of prior natalizumab doses, n (%) | |
| 0 | 2058 (42.7) |
| 1 | 1089 (22.6) |
| 2 | 875 (18.1) |
| 3 | 799 (16.6) |
| Enrolment by country, n (%) | |
| Germany (130 sites) | 1430 (29.7) |
| Czech Republic (15 sites) | 644 (13.4) |
| Belgium (34 sites) | 563 (11.7) |
| Italy (17 sites) | 314 (6.5) |
| Canada (19 sites) | 291 (6.0) |
| The Netherlands (22 sites) | 268 (5.6) |
| Norway (13 sites) | 200 (4.1) |
| France (65 sites) | 188 (3.9) |
| Finland (7 sites) | 183 (3.8) |
| Australia (12 sites) | 179 (3.7) |
| Slovakia (5 sites) | 141 (2.9) |
| Greece (12 sites) | 129 (2.7) |
| Great Britain (14 sites) | 119 (2.5) |
| Spain (13 sites) | 99 (2.1) |
| Portugal (8 sites) | 67 (1.4) |
| Argentina (3 sites) | 6 (0.1) |
| Number of patients dosed with natalizumab, n (%) | 4821 (100) |
| Number of patients who discontinued natalizumab,* n (%) | 1222 (25.3) |
| Reasons for natalizumab discontinuation,† n (%) | |
| Anti-JCV antibody positive | 277 (5.7) |
| Medication change‡ | 247 (5.1) |
| Insufficient efficacy | 229 (4.8) |
| Patient decision | 171 (3.5) |
| Withdrawal of consent | 142 (2.9) |
| Adverse event (non-serious adverse event) | 107 (2.2) |
| Physician decision | 97 (2.0) |
| Pregnancy/pregnancy desire | 74 (1.5) |
| Tolerability problem | 65 (1.3) |
| Natalizumab treatment duration concern | 65 (1.3) |
| Serious adverse event | 51 (1.1) |
| Antibodies to natalizumab | 44 (0.9) |
| Other reason | 35 (0.7) |
| Non-compliance | 31 (0.6) |
| Prior IS use | 28 (0.6) |
| Safety concern | 26 (0.5) |
| Lost to follow-up | 24 (0.5) |
| PML§ | 7 (0.1) |
| Malignancy/cancer | 7 (0.1) |
| Moved out of area | 5 (0.1) |
| Inconvenience | 5 (0.1) |
| Other serious infection | 4 (<0.1) |
| No reason given in data | 3 (<0.1) |
| Death | 2 (<0.1) |
| Opportunistic infection | 1 (<0.1) |
| Number of patients who withdrew from TOP† | 740 (15.3) |
| Reasons for withdrawal from TOP, n (%) | |
| Lost to follow-up | 121 (2.5) |
| Medication change‡ | 116 (2.4) |
| Patient decision | 115 (2.4) |
| Withdrawal of consent | 110 (2.3) |
| Moved out of the area | 99 (2.1) |
| Anti-JCV antibody | 62 (1.3) |
| Physician decision | 52 (1.1) |
| Insufficient efficacy | 46 (1.0) |
| Adverse event (non-serious adverse event) | 43 (0.9) |
| Inconvenience | 39 (0.8) |
| Serious adverse event | 34 (0.7) |
| Other reason | 32 (0.7) |
| Pregnancy/pregnancy desire | 27 (0.6) |
| Natalizumab antibody positive | 20 (0.4) |
| Non-compliance | 13 (0.3) |
| Safety concern | 11 (0.2) |
| Tolerability problem | 8 (0.2) |
| Prior IS use | 8 (0.2) |
| Death | 2 (<0.1) |
| PML | 2 (<0.1) |
| Other serious infection | 2 (<0.1) |
| No reason given in data | 2 (<0.1) |
| Malignancy/cancer | 1 (<0.1) |
*Of the 1222 patients who discontinued natalizumab, 223 (18.3%) discontinued after 1–6 doses, 213 (17.4%) discontinued after 7–12 doses, 152 (12.4%) discontinued after 13–18 doses, 188 (15.4%) discontinued after 19–24 doses, 209 (17.1%) discontinued after 25–30 doses and 237 (19.4%) discontinued after >30 doses.
†Patients could have more than one reason for discontinuation/withdrawal recorded.
‡Medication changes were primarily to other DMTs.
§Although PML was cited as the reason for discontinuation in only seven PML cases, natalizumab was discontinued in all 18 cases upon suspicion of PML. Diagnosis was made days to weeks after the last dose.
DMT, disease-modifying therapy; IS, immunosuppressant; JCV, JC virus; PML, progressive multifocal leucoencephalopathy; TOP, Tysabri Observational Program.