Table 2.
Safety summary in the overall population and by prior enrollment status.
| AE, n (%) | Overall population n = 1057 |
De novo enrollment n = 593 |
EVOLVE-MS-2 rollover | |
|---|---|---|---|---|
| Prior DMF n = 225 |
Prior DRF n = 239 |
|||
| Any AE | 938 (88.7) | 519 (87.5) | 207 (92.0) | 212 (88.7) |
| Mild | 306 (28.9) | 170 (28.7) | 70 (31.1) | 66 (27.6) |
| Moderate | 532 (50.3) | 297 (50.1) | 112 (49.8) | 123 (51.5) |
| Severe | 100 (9.5) | 52 (8.8) | 25 (11.1) | 23 (9.6) |
| AEs leading to treatment discontinuation | 85 (8.0) | 49 (8.3) | 13 (5.8) | 23 (9.6) |
| Most common AEs leading to treatment discontinuation (occurring in ⩾0.5% of patients) | ||||
| Lymphopenia | 14 (1.3) | 6 (1.0) | 3 (1.3) | 5 (2.1) |
| MS relapse | 11 (1.0) | 7 (1.2) | 0 | 4 (1.7) |
| GI disorders a | 7 (0.7) | 5 (0.8) | 1 (0.4) | 1 (0.4) |
| Lymphocyte count decreased | 7 (0.7) | 1 (0.2) | 1 (0.4) | 5 (2.1) |
| Flushing | 5 (0.5) | 2 (0.3) | 1 (0.4) | 2 (0.8) |
| Any SAE | 123 (11.6) | 69 (11.6) | 25 (11.1) | 29 (12.1) |
| Most common SAEs (occurring in ⩾0.5% of patients) | ||||
| Nervous system disorders b | 68 (6.4) | 35 (5.9) | 13 (5.8) | 20 (8.4) |
| MS relapse c | 61 (5.8) | 32 (5.4) | 10 (4.4) | 19 (7.9) |
| GI disorder b | 10 (0.9) | 5 (0.8) | 3 (1.3) | 2 (0.8) |
| Injury, poisoning, and procedural complications b | 10 (0.9) | 7 (1.2) | 3 (1.3) | 0 |
| Infections and infestations b | 9 (0.9) | 4 (0.7) | 3 (1.3) | 2 (0.8) |
| Reproductive system and breast disorders b | 7 (0.7) | 5 (0.8) | 1 (0.4) | 1 (0.4) |
| Cardiac disorders b | 6 (0.6) | 3 (0.5) | 1 (0.4) | 2 (0.8) |
| Death d | 4 (0.4) | 3 (0.5) | 0 | 1 (0.4) |
| Most common AEs (occurring in ⩾10% of patients cumulatively) | ||||
| Flushing | 288 (27.2) | 226 (38.1) | 29 (12.9) | 33 (13.8) |
| MS relapse | 206 (19.5) | 113 (19.1) | 45 (20.0) | 48 (20.1) |
| Upper respiratory tract infection | 153 (14.5) | 76 (12.8) | 35 (15.6) | 42 (17.6) |
| Nasopharyngitis | 137 (13.0) | 86 (14.5) | 27 (12.0) | 24 (10.0) |
| Lymphopenia | 124 (11.7) | 51 (8.6) | 38 (16.9) | 35 (14.6) |
| Diarrhea | 109 (10.3) | 66 (11.1) | 25 (11.1) | 18 (7.5) |
| AEs of special interest (category) e | ||||
| Lymphopenia (SMQ hematopoietic leukopenia) | 187 (17.7) | 82 (13.8) | 56 (24.9) | 49 (20.5) |
| Lymphopenia (lymphocyte relevant) | 163 (15.4) | 68 (11.5) | 48 (21.3) | 47 (19.7) |
| Cardiac disorders f | 145 (13.7) | 70 (11.8) | 38 (16.9) | 37 (15.5) |
| Liver injury | 79 (7.5) | 39 (6.6) | 19 (8.4) | 21 (8.8) |
| Renal injury | 37 (3.5) | 13 (2.2) | 10 (4.4) | 14 (5.9) |
| Infections g | 16 (1.5) | 7 (1.2) | 4 (1.7) | 5 (2.1) |
| Malignancies | 5 (0.5) | 1 (0.2) | 1 (0.4) | 3 (1.3) |
AE: adverse event; DMF: dimethyl fumarate; DRF: diroximel fumarate; MS: multiple sclerosis; GI: gastrointestinal; SAE: serious adverse event; SMQ: standardized MedDRA query.
Diarrhea (n = 3); anal incontinence, dyspepsia, irritable bowel syndrome, and peptic ulcer (all n = 1).
System organ class.
Preferred term.
Accidental fall, bacterial pneumonia, hypertensive heart disease, and cardiac arrest; none of the deaths were considered related to the study drug by the investigator.
AEs of special interest included anaphylaxis and angioedema (serious), cardiac disorders, lymphopenia (SMQ hematopoietic leukopenia) and lymphopenia (lymphocyte relevant), liver injury, renal injury, GI tolerability AEs (serious or leading to discontinuation), abuse potential, and pancreatitis.
Within the cardiac disorders category, the most common AE was dizziness (57/1057; 5.4%).
Includes opportunistic infections (AEs and SAEs) and all serious infections (including serious opportunistic infections).