Clinical Neurology · Neuro-Immunology
MS DMT Efficacy & PML Risk
Comparative efficacy of disease-modifying therapies (DMTs) versus placebo, and PML risk stratification for natalizumab (Tysabri) based on treatment duration, prior immunosuppressant use, and JCV antibody status.
Efficacy of DMT against placebo after one year of therapy
Rough estimates; cannot be directly compared across studies.
| Drug | Annualized relapse rate | EDSS progression | New MRI lesions | Relapse free (2 ys) | Study |
|---|---|---|---|---|---|
| Placebo | 45% | 13% | 8.1 | ||
| Avonex | 33% | 36% | INCOMIN | ||
| Betaseron | 36% | 13% (2 ys) | 3.3 | 51% | INCOMIN |
| Rebif | 29% | 15.2% | 56% | ||
| Copaxone | 34% | 3.3 | 59% | BEYOND | |
| Gilenya | 20% | ||||
| Tecfidera | 17% | 16% | 2.6 | ||
| Lemtrada | 18% | 8% (2 ys) | 78% | ||
| Tysabri | 22% | 0 | MS1 | ||
| Zinbryta | 21% | 6% | 2.4 | ||
| Ocrevus | 15% | 9.8% | OPERA I, II |
PML risk with Tysabri
Three factors increase the risk:
- Treatment > 2 years
- JCV Ab negative: < 1/1000
- JCV Ab positive:
- 1–24 months: <1/1000
- 25–48 months: 3/1000
- 49–72 months: 6/1000
- Seroconversion rate is 3–6% annually
- Prior treatment with immunosuppressants (MTX, cyclophosphamide)
- JCV antibodies (risk by antibody index, see below)
| Antibody index | 1–24 months | 25–48 months | 49–72 months |
|---|---|---|---|
| ≤ 0.9 | 1/10,000 | 3/10,000 | 4/10,000 |
| ≤ 1.1 | 1/10,000 | 7/10,000 | 7/10,000 |
| ≤ 1.3 | 1/10,000 | 1/1,000 | 1.2/1,000 |
| ≤ 1.5 | 1/10,000 | 1.2/1,000 | 1.3/1,000 |
| > 1.5 | 1/1,000 | 8.1/1,000 | 8.5/1,000 |
Ahmed Koriesh, MD