Table 1.
The main findings from randomized control trials of disease-modifying therapies in multiple sclerosis*
| Drug (study) | Comparator | Number of pwMS (study drug/comparator) | Relapse rate reduction (%) | Reduction of the progression (%) | Reduction of the MRI activity (%) | Side-effects | The need for regular monitoring |
|---|---|---|---|---|---|---|---|
|
Platform therapies – maintenance therapies
| |||||||
| Interferon beta 1 a (MSCRG study) (43) |
Placebo |
301 |
32 |
37 |
27 (NS) |
Injection site reactions, flu-like symptoms, elevated liver enzymes, depression |
Not necessary |
| Interferon beta 1a (PRIMSM study) (44) |
Placebo |
560 |
33 |
31 |
78 |
Injection site reactions, flu-like symptoms, elevated liver enzymes, depression |
Not necessary |
| Interferon beta 1b (MSSG study) (45) |
Placebo |
372 |
34 |
29 |
83 |
Injection site reactions, flu-like symptoms, elevated liver enzymes, depression |
Not necessary |
| Glatiramer acetate (CMSSG study) (46) |
Placebo |
251 |
29 |
12 (NS) |
35 |
Injection site reactions, flu-like symptoms, systematic reaction to drug administration |
Not necessary |
| Teriflunomide (TEMSO TOWER study) (47,48) |
Placebo |
1086/1165 |
37/32 |
30/33 |
69/NA |
Gastrointestinal symptoms, hair thinning or decreased hair density, rash, elevated liver enzymes, peripheral neuropathy |
Blood pressure, CBC, liver enzymes before the treatment, during the first six months liver enzymes every two weeks, and after that every six weeks |
| Dimethyl fumarate (DEFINE/CONFIRM study) (49,50) |
Placebo/glatiramer acetate |
1237/1430 |
53/44 |
38/21 (NS) |
85/71 |
Flushing, gastrointestinal symptoms, progressive multifocal leukoencephalopathy (rarely) |
Differential blood count before the treatment, and after every two-three months (PML risk – lymphocytes <0.5× 109/L) |
|
High-efficacy therapies – maintenance therapies
| |||||||
| Natalizumab (AFFIRM study) (51) |
Placebo |
942 |
68 |
54 |
83 |
Infusion reactions, infections, progressive multifocal leukoencephalopathy |
JCV titer every 6 months, MR every 3-6 months for patients with JCV positive titer after the second year of treatment |
| Fingolimod (FREEDOMS 1/2 study) (52,53) |
Placebo |
1272/1083 |
54/50 |
37/28 (NS) |
75/74 |
Bradycardia, AV block, macular edema, increased infection risk (especially VZV) progressive multifocal leukoencephalopathy |
Before the treatment: ECG, optic fundus or OCT, CBC, VZV (if the patient was not previously infected); after the treatment: CBC regularly (lymphocytes should be >0.2 × 109/l), optic fundus/OCT after three months |
| Ozanimod (RADIANCE and SUNBEAM) (54,55) |
Interferon beta 1a s.c. |
1320/1346 |
38/48 |
5 (Pooled analysis, NS) |
42/48 |
Bradycardia, macular edema, increased infection risk (especially VZV) progressive multifocal leukoencephalopathy |
Before the treatment: ECG, optic fundus or OCT, CBC, VZV (if the patient was not previously infected); after the treatment: CBC regularly (lymphocytes should be >0.2 × 109/l), optic fundus/OCT after three months |
| Ponesimod (OPTIMUM) (56) |
Teriflunomide |
567 |
31 |
17 (NS) |
56 |
Bradycardia, AV block, macular edema, increased infection risk (especially VZV) progressive multifocal leukoencephalopathy |
Before the treatment: ECG, optic fundus or OCT, CBC, VZV (if the patient was not previously infected); after the treatment: CBC regularly (lymphocytes should be >0.2 × 109/l), optic fundus/OCT after three months |
| Ocrelizumab (OPERA I and II studies) (57) |
Interferon beta 1a s.c. |
821/835 |
46/47 |
40 (pooled results) |
77/83 |
Infusion reactions, increased infection risk, increased risk of tumors? |
CBC, IgG and IgM every six months |
| Ofatumumab (ASCLEPIOS I and II) (58) |
Teriflunomide |
927/955 |
51/59 |
33 (pooled results) |
82/85 |
Injection reactions, increased infection risk, increased risk of tumors? |
CBC, IgG and IgM before every treatment dose |
|
High-efficacy therapies – Immunoreconstitutional therapies
| |||||||
| Alemtuzumab (CARE – MS I/CARE – MS II studies) (59,60) |
Interferon beta 1a s.c. |
578/628 |
55/48 |
30 (NS)/41 |
16/62 |
Infusion reactions, autoimmune thyroid disease, idiopathic thrombocytopenic purpura, glomerulonephritis, infections |
During the treatment and four years after the last treatment dose: CBC, creatinine and urine once a month, TSH every three months |
| Cladribine (CLARITY study) (61) | Placebo | 1326 | 57.6 | 33 | 73.4 | Increased infection risk, increased risk of tumors? | Lymphocytes before the treatment, and 2 and 6 months after the beginning of treatment every year |
*Abbreviations: pwMS – people with multiple sclerosis; MRI – magnetic resonance imaging; CBC – complete blood count; PML – progressive multifocal leukoencephalopathy; JCV – John Cunningham virus, IgG – immunoglobulin G; IgM – immunoglobulin M; OCT – optic coherence tomography; TSH – thyroid stimulating hormone; VZV – varicella zoster virus, s.c. – subcutaneous; NS – not significant.