Table 2.
Cases Referred to the Independent Adjudication Committee (IAC) for Evaluation for Progressive Multifocal Leukoencephalopathy (PML).*
| Case No. | Diagnosis | Source of Referral | Findings on Neurologic Examination | Findings on MRI | Findings on Follow-up MRI | Results of CSF Testing for JCV DNA | Determination by IAC |
|---|---|---|---|---|---|---|---|
| Index cases | |||||||
| IAC-991 | MS | Physician | Deteriorating | Possible PML | Progressive | Detected | PML confirmed |
| IAC-992 | MS | Physician | Deteriorating | Possible PML | Progressive | Detected | PML confirmed |
| IAC-993 | CD | Retrospective review of serious adverse events | Deteriorating | Possible PML | Progressive | No sample available | PML confirmed |
| Cases evaluated by the IAC | |||||||
| 1 | CD | Central reader | Normal | Not PML | Not detected | PML ruled out | |
| 2 | CD | Local reader | Normal | Not PML | Not detected | PML ruled out | |
| 3 | CD | Central reader | Normal | Not PML | Not detected | PML ruled out | |
| 4 | CD | Central reader | Normal | Not PML | Not detected | PML ruled out | |
| 5 | MS | Physician | Stable | Not PML | Not detected | PML ruled out | |
| 6 | CD | Central reader | Stable | Not PML | Not detected | PML ruled out | |
| 7 | CD | Central reader | Stable | Not PML | Not detected | PML ruled out | |
| 8 | MS | Physician | Progressive (MS) | Possible PML | Not PML | Not detected† | PML ruled out |
| 9 | MS | Physician | Progressive (MS) | Not PML | Not PML | Not detected | PML ruled out |
| 10 | MS | Central reader | Progressive (MS) | Possible PML | Not PML | Not detected | PML ruled out |
| 11 | RA | Central reader | Mild vestibular dysfunction | Possible PML | Not PML | Not detected | PML ruled out |
| 12 | CD | Central reader | Normal | Possible PML | Not PML | Not detected | PML ruled out |
| 13 | CD | Local and central readers | Normal | Possible PML | Not PML | Not detected | PML ruled out |
| 14 | CD | Central reader | Normal | Possible PML | Not PML | Not detected | PML ruled out |
| 15 | CD | Central reader | Mild cognitive changes | Possible PML | Not PML | Not detected | PML ruled out |
| 16 | Pediatric MS | Sponsor | Progressive (MS) | Not PML | Not PML | No sample available | PML ruled out |
| 17 | MS | Physician | Progressive (MS) | Not PML | Not PML | No sample available | PML ruled out |
| 18 | MS | Physician | Progressive (MS) | Not PML | Not PML | No sample available | PML ruled out |
| 19 | CD | Central reader | Normal | Possible PML | Not PML | No sample available | PML ruled out |
| 20 | CD | Central reader | Normal | Possible PML | Not PML | No sample available | PML ruled out |
| 21 | CD | Central reader | Normal | Possible PML | Not PML | No sample available | PML ruled out |
| 22 | CD | Central reader | Normal | Possible PML | Not PML | No sample available | PML ruled out |
| 23 | CD | Central reader | Normal | Not PML | Not PML | No sample available | PML ruled out |
| 24‡ | MS | Physician | Stable | Not PML | No sample available | PML ruled out | |
| 25 | CD | Central reader | Stable | Not PML | No sample available | PML ruled out | |
| 26 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 27 | CD | Central reader | Remote optic neuritis | Not PML | No sample available | PML ruled out | |
| 28 | CD | Sponsor (because of high serum titers of JCV) | Stable | Not PML | No sample available | PML ruled out | |
| 29 | RA | Central reader | Reflex asymmetry | Not PML | No sample available | PML ruled out | |
| 30 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 31 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 32 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 33 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 34‡ | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 35 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 36 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 37 | RA | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 38 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 39 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 40 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 41 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 42 | CD | Central reader | Normal | Not PML | No sample available | PML ruled out | |
| 43 | CD | MRI precluded§ | Normal | NA | Not detected | PML ruled out | |
| 44 | MS | Physician | Progressive lesions documented over 5 yr (antedating receipt of natalizumab) | Possible PML | No sample available | Indeterminate | |
*
MRI denotes magnetic resonance imaging, CSF cerebrospinal fluid, JCV JC virus, MS multiple sclerosis, CD Crohn's disease, RA rheumatoid arthritis, and NA not available.
†
Results of repeated testing of CSF were negative for PML.
‡
The patient received placebo.
§
MRI was precluded because of the size of the patient.