TABLE 4.
The signal strength of the top 20 adverse events (AEs) of S1PR modulators.
| SOC | PT | N | PRR (χ2) | ROR (95% CI) | IC |
|---|---|---|---|---|---|
| Fingolimod | |||||
| Nervous system disorders | Hemihyperaesthesia | 3 | 154.16 (228.26) | 154.17 (31.12-763.85) | 6.28 |
| Endocrine disorders | Haemorrhagic adrenal infarction | 4 | 102.78 (241.89) | 102.78 (29.00-364.22) | 5.96 |
| Infections and infestations | Osseous cryptococcosis a | 3 | 66.07 (134.58) | 66.07 (17.08-255.51) | 5.54 |
| Investigations | Vibration test abnormal | 8 | 61.67 (341.04) | 61.67 (27.16-140.01) | 5.47 |
| Investigations | JC polyomavirus test positive a | 449 | 58.41 (18,375.62) | 58.51 (52.48-65.22) | 5.41 |
| Investigations | CD30 expression a | 10 | 53.16 (380.56) | 53.16 (25.91-109.08) | 5.31 |
| Investigations | Lymphocyte count decreased a | 3,411 | 53.03 (129,602.68) | 53.68 (51.62-55.82) | 5.31 |
| Nervous system disorders | Hoffmann’s sign | 11 | 49.88 (398.08) | 49.88 (25.27-98.44) | 5.25 |
| Nervous system disorders | Gait spastic | 64 | 48.60 (2,268.70) | 48.61 (36.71-64.39) | 5.22 |
| Investigations | ECG signs of myocardial infarction a | 4 | 47.44 (139.04) | 47.44 (15.47-145.48) | 5.19 |
| Eye disorders | Macular oedema a | 865 | 47.27 (29,986.50) | 47.42 (43.93-51.17) | 5.19 |
| Nervous system disorders | Central nervous system lesion a | 2,739 | 46.86 (94,300.08) | 47.32 (45.33-49.39) | 5.18 |
| Investigations | Dermatologic examination abnormal a | 3 | 46.25 (102.16) | 46.25 (12.73-168.05) | 5.16 |
| Skin and subcutaneous tissue disorders | Lentigo | 69 | 45.27 (2,308.91) | 45.28 (34.62-59.22) | 5.14 |
| Infections and infestations | Cryptococcal cutaneous infection a | 22 | 45.22 (735.59) | 45.22 (28.12-72.74) | 5.14 |
| Neoplasms benign, malignant and unspecified | Haemangioma of skin a | 65 | 43.95 (2,123.02) | 43.96 (33.37-57.91) | 5.11 |
| Nervous system disorders | Lhermitte’s sign | 50 | 43.80 (1,628.38) | 43.80 (32.00-59.97) | 5.10 |
| Investigations | Tandem gait test abnormal | 12 | 40.22 (363.95) | 40.22 (21.31-75.92) | 5.00 |
| Neoplasms benign, malignant and unspecified | Fibrous histiocytoma a | 50 | 38.73 (1,468.95) | 38.74 (28.41-52.83) | 4.96 |
| Investigations | Romberg test positive | 25 | 38.54 (731.34) | 38.54 (24.87-59.75) | 4.96 |
| Siponimod | |||||
| Investigations | Lipids decreased | 3 | 125.16 (348.18) | 125.18 (39.01-401.63) | 6.88 |
| Investigations | Lymphocyte count a decreased | 307 | 48.20 (13,867.67) | 48.90 (43.63-54.81) | 5.56 |
| Investigations | Lymphocyte count abnormal a | 16 | 45.24 (677.21) | 45.27 (27.58-74.31) | 5.47 |
| Blood and lymphatic system disorders | Lymphopenia a | 142 | 30.70 (4,021.22) | 30.91 (26.17-36.50) | 4.92 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Bowen’s disease a | 13 | 29.79 (356.55) | 29.81 (17.24-51.55) | 4.88 |
| Eye disorders | Macular oedema a | 51 | 28.68 (1,343.79) | 28.75 (21.80-37.91) | 4.82 |
| Renal and urinary disorders | Urinary tract inflammation | 3 | 24.63 (67.20) | 24.63 (7.89-76.90) | 4.61 |
| Nervous system disorders | Gait spastic | 3 | 23.23 (63.10) | 23.23 (7.44-72.51) | 4.52 |
| Vascular disorders | Hypertensive urgency a | 3 | 22.55 (61.10) | 22.55 (7.23-70.36) | 4.48 |
| Nervous system disorders | Paresis | 16 | 22.25 (321.24) | 22.27 (13.60-36.45) | 4.46 |
| Cardiac disorders | Atrioventricular block first degree a | 29 | 20.46 (531.58) | 20.49 (14.21-29.55) | 4.34 |
| Nervous system disorders | Uhthoff’s phenomenon | 6 | 20.01 (107.30) | 20.01 (8.96-44.73) | 4.31 |
| Nervous system disorders | Paraparesis | 11 | 19.20 (188.04) | 19.21 (10.61-34.79) | 4.25 |
| Nervous system disorders | Dysmetria | 4 | 18.17 (64.33) | 18.17 (6.79-48.64) | 4.17 |
| Nervous system disorders | Band sensation | 9 | 17.21 (136.28) | 17.22 (8.93-33.19) | 4.09 |
| Nervous system disorders | Electric shock sensation | 10 | 17.21 (151.39) | 17.22 (9.24-32.08) | 4.09 |
| Nervous system disorders | Trigeminal neuralgia a | 26 | 17.20 (393.31) | 17.22 (11.70-25.33) | 4.09 |
| Eye disorders | Amblyopia | 3 | 16.85 (44.36) | 16.85 (5.41-52.50) | 4.06 |
| Investigations | Heart rate decreased a | 179 | 14.62 (2,256.09) | 14.74 (12.71-17.08) | 3.86 |
| Investigations | JC polyomavirus test positive a | 11 | 13.86 (130.32) | 13.86 (7.66-25.08) | 3.78 |
| Ozanimod | |||||
| Investigations | Lymphocyte count abnormal a | 7 | 38.17 (251.01) | 38.20 (18.14-80.43) | 5.24 |
| Blood and lymphatic system disorders | Lymphopenia a | 48 | 20.07 (865.54) | 20.15 (15.17-26.78) | 4.32 |
| Investigations | Lymphocyte count decreased a | 66 | 19.87 (1,177.14) | 19.98 (15.68-25.47) | 4.31 |
| Reproductive system and breast disorders | Uterine disorder | 6 | 14.26 (73.70) | 14.26 (6.40-31.80) | 3.83 |
| Nervous system disorders | Head titubation | 3 | 12.53 (31.72) | 12.53 (4.03-39.93) | 3.64 |
| Reproductive system and breast disorders | Penile swelling | 3 | 12.37 (31.26) | 12.38 (3.98-38.44) | 3.62 |
| Eye disorders | Macular oedema a | 11 | 11.95 (110.04) | 11.96 (6.62-21.62) | 3.57 |
| Ear and labyrinth disorders | Auditory disorder | 3 | 11.92 (29.91) | 11.92 (3.84-37.03) | 3.57 |
| Cardiac disorders | Cardiac flutter a | 13 | 11.70 (126.80) | 11.71 (6.79-20.19) | 3.54 |
| Nervous system disorders | Optic neuritis | 17 | 10.63 (147.94) | 10.65 (6.61-17.14) | 3.41 |
| Nervous system disorders | Sleep deficit | 3 | 10.60 (26.01) | 10.60 (3.41-32.92) | 3.40 |
| Nervous system disorders | Brain fog | 3 | 10.01 (24.28) | 10.02 (3.23-31.10) | 3.32 |
| Neoplasms benign, malignant and unspecified | Papillary thyroid cancer | 3 | 10.00 (24.23) | 10.00 (3.22-31.05) | 3.32 |
| Investigations | Heart rate decreased a | 62 | 9.84 (491.55) | 9.89 (7.70-12.70) | 3.30 |
| Investigations | JC polyomavirus test positive a | 4 | 9.80 (31.52) | 9.80 (3.67-26.15) | 3.29 |
| Nervous system disorders | Peroneal nerve palsy | 10 | 9.64 (77.28) | 9.65 (5.19-17.95) | 3.27 |
| Blood and lymphatic system disorders | Lymph node pain | 3 | 9.17 (21.79) | 9.17 (2.95-28.48) | 3.19 |
| Immune system disorders | Multiple allergies a | 12 | 8.71 (81.77) | 8.72 (4.95-15.37) | 3.12 |
| Eye disorders | Periorbital swelling | 6 | 8.31 (38.49) | 8.31 (3.73-18.52) | 3.05 |
| Renal and urinary disorders | Bladder disorder | 14 | 7.84 (83.37) | 7.85 (4.64-13.26) | 2.97 |
a
Adverse events mentioned in the instructions of fingolimod, siponimod and ozanimod, respectively.