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Table 2 Adverse events and first-dose monitoring events during the extension study

From: Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study

 

Placebo-fingolimod 0.5 mg

(n = 27)

Placebo-fingolimod 1.25 mg

(n = 23)

Fingolimod 0.5 mg

(n = 47)

Fingolimod 1.25 mg

(n = 46)

Total

(n = 143)

Any AE

27 (100)

23 (100)

45 (95.7)

44 (95.7)

139 (97.2)

AEs leading to study drug discontinuationa

8 (29.6)

5 (21.7)

7 (14.9)

2 (4.3)

22 (15.4)

SAEs

1 (3.7)

5 (21.7)

8 (17.0)

5 (10.9)

19 (13.3)

SAEs leading to study drug discontinuationb

1 (3.7)

1 (4.3)

3 (6.4)

0 (0.0)

5 (3.5)

Frequent or special-interest adverse events

     

Infections and infestations

22 (81.5)

17 (73.9)

37 (78.7)

38 (82.6)

114 (79.7)

 Total upper respiratory tract infections

17 (63.0)

12 (52.2)

31 (66.0)

29 (63.0)

89 (62.2)

  Nasopharyngitis

15 (55.6)

12 (52.2)

29 (61.7)

28 (60.9)

84 (58.7)

  Pharyngitis

1 (3.7)

2 (8.7)

5 (10.6)

4 (8.7)

12 (8.4)

  Upper respiratory tract infection

1 (3.7)

0 (0.0)

2 (4.3)

1 (2.2)

4 (2.8)

 Influenza viral infections

2 (7.4)

3 (13.0)

3 (6.4)

6 (13.0)

14 (9.8)

 Lower respiratory tract and lung infections

1 (3.7)

0 (0.0)

1 (2.1)

2 (4.3)

4 (2.8)

  Bronchitis

1 (3.7)

0 (0.0)

1 (2.1)

2 (4.3)

4 (2.8)

 Herpes viral infections

2 (7.4)

4 (17.4)

1 (2.1)

3 (6.5)

10 (7.0)

  Herpes zoster

1 (3.7)

2 (8.7)

1 (2.1)

1 (2.2)

5 (3.5)

  Oral herpes

0 (0.0)

2 (8.7)

0 (0.0)

0 (0.0)

2 (1.4)

 Urinary tract infections

2 (7.4)

1 (4.3)

4 (8.5)

9 (19.6)

16 (11.2)

  Cystitis

2 (7.4)

1 (4.3)

3 (6.4)

7 (15.2)

13 (9.1)

Vascular disorders

1 (3.7)

1 (4.3)

4 (8.5)

2 (4.3)

8 (5.6)

 Hypertension

0 (0.0)

1 (4.3)

3 (6.4)

1 (2.2)

5 (3.5)

Eye disorders

5 (18.5)

3 (13.0)

14 (29.8)

9 (19.6)

31 (21.7)

 Macular edema

0 (0.0)

0 (0.0)

1 (2.1) c

0 (0.0)

1 (0.7)

Nervous system disorders

4 (14.8)

6 (26.1)

14 (29.8)

9 (19.6)

33 (23.1)

 Headache

1 (3.7)

3 (13.0)

8 (17.0)

3 (6.5)

15 (10.5)

Investigations

13 (48.1)

14 (60.9)

15 (31.9)

17 (37.0)

59 (41.3)

 Abnormal liver function test

7 (25.9)

9 (39.1)

6 (12.8)

8 (17.4)

30 (21.0)

 Alanine aminotransferase increased

2 (7.4)

0 (0.0)

0 (0.0)

1 (2.2)

3 (2.1)

 Gamma-glutamyl transferase increased

1 (3.7)

2 (8.7)

1 (2.1)

0 (0.0)

4 (2.8)

 Aspartate amino-transferase increased

1 (3.7)

0 (0.0)

0 (0.0)

1 (2.2)

2 (1.4)

 Hepatic enzyme increased

1 (3.7)

1 (4.3)

1 (2.1)

0 (0.0)

3 (2.1)

 Lymphocyte count decreased

3 (11.1)

2 (8.7)

3 (6.4)

2 (4.3)

10 (7.0)

Gastrointestinal disorders

11 (40.7)

6 (26.1)

22 (46.8)

23 (50.0)

62 (43.4)

 Stomatitis

4 (14.8)

1 (4.3)

4 (8.5)

6 (13.0)

15 (10.5)

 Diarrhea

1 (3.7)

2 (8.7)

3 (6.4)

6 (13.0)

12 (8.4)

 Constipation

1 (3.7)

0 (0.0)

5 (10.6)

2 (4.3)

8 (5.6)

Skin and subcutaneous tissue disorders

8 (29.6)

9 (39.1)

14 (29.8)

16 (34.8)

47 (32.9)

 Rash

3 (11.1)

4 (17.4)

1 (2.1)

0 (0.0)

8 (5.6)

Blood and lymphatic system disorders

7 (25.9)

5 (21.7)

10 (21.3)

13 (28.3)

35 (24.5)

 Lymphopenia

2 (7.4)

3 (13.0)

6 (12.8)

8 (17.4)

19 (13.3)

 Leukopenia

4 (14.8)

1 (4.3)

2 (4.3)

5 (10.9)

12 (8.4)

Respiratory, thoracic and mediastinal disorders

1 (3.7)

4 (17.4)

6 (12.8)

9 (19.6)

20 (14.0)

Metabolism and nutrition disorders

4 (14.8)

1 (4.3)

4 (8.5)

7 (15.2)

16 (11.2)

 Hyperlipidemia

2 (7.4)

0 (0.0)

2 (4.3)

5 (10.9)

9 (6.3)

Psychiatric disorders

2 (7.4)

2 (8.7)

8 (17.0)

4 (8.7)

16 (11.2)

Neoplasms benign, malignant and unspecified (including cysts and polyps)

0 (0.0)

1 (4.3)

9 (19.1)

1 (2.2)

11 (7.7)

 Skin papilloma

0 (0.0)

0 (0.0)

6 (12.8)

0 (0.0)

6 (4.2)

First-dose monitoring eventsd

     

Cardiac disorders

4 (14.8)

7 (30.4)

0 (0.0)

0 (0.0)

11 (7.7)

 Atrioventricular block second degree

0 (0.0)

3 (13.0)

0 (0.0)

0 (0.0)

3 (2.1)

 Bradycardia

0 (0.0)

3 (13.0)

0 (0.0)

0 (0.0)

3 (2.1)

Serious adverse eventse

     

Infections and infestations

0 (0.0)

0 (0.0)

0 (0.0)

2 (4.3)

2 (1.4)

 Appendicitis

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.2)

1 (0.7)

 Urinary tract infection

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.2)

1 (0.7)

Cardiac disorders

0 (0.0)

2 (8.7)

0 (0.0)

0 (0.0)

2 (1.4)

 Bradycardia

0 (0.0)

2 (8.7)

0 (0.0)

0 (0.0)

2 (1.4)

Neoplasms benign, malignant and unspecified (including cysts and polyps)

0 (0.0)

0 (0.0)

2 (4.3)

0 (0.0)

2 (1.4)

 Breast cancer

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

1 (0.7)

 CNS lymphoma

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

1 (0.7)

Nervous system disorders

1 (3.7)

2 (8.7)

3 (6.4)

1 (2.2)

7 (4.9)

 Status epilepticus

0 (0.0)

0 (0.0)

0 (0.0)

1 (2.2)

1 (0.7)

 Convulsion

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

1 (0.7)

 Leukoencephalopathy

0 (0.0)

1 (4.3)

0 (0.0)

0 (0.0)

1 (0.7)

 Multiple sclerosis relapse

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

1 (0.7)

 Myoclonus

0 (0.0)

0 (0.0)

1 (2.1)

0 (0.0)

1 (0.7)

 Neuromyelitis optica

1 (3.7)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.7)

 Radiculitis

0 (0.0)

1 (4.3)

0 (0.0)

0 (0.0)

1 (0.7)

  1. Data are patients (n [%]) in whom events were reported by at least 10% of patients in one or more treatment group, or were events of special interest. Adverse events listed are classified as system organ class (e.g. infections) followed by high-level term (e.g. total upper respiratory tract infections) and/or preferred term (e.g. upper respiratory tract infection, nasopharyngitis, sinusitis) for the event, as applicable
  2. Abbreviations: AE Adverse event, AQP4 Aquaporin-4, CNS Central nervous system, FDM, first dose monitoring, SAE Serious adverse event
  3. aAny AE leading to study drug discontinuation includes any patient whose primary or secondary reason for discontinuing the study drug was an AE
  4. bSAEs leading to study drug discontinuation were neoplasms (breast cancer and CNS lymphoma), and nervous system disorders (MS relapse, leukoencephalopathy and neuromyelitis optica). Leukoencephalopathy and neuromyelitis optica were reported in patients who were anti-AQP4 antibody-positive
  5. cNot confirmed on central review by a retina specialist from the data and safety monitoring board
  6. dFDM events for placebo-fingolimod switch groups on entry to the extension study
  7. eSAE data are n (%) for events reported by at least two patients in one or more treatment group, unless otherwise stated