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Table 2 Pooled safety outcomes across indications

From: Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials

 

Pooled PsO IXE (N = 6892)

Pooled PsA IXE (N = 1401)

Pooled axSpA IXE (N = 932)

Total patient-years

18025.7

2247.7

2097.7

Maximum exposure (days)

2236

1219

1241

 

n (%)

IR

95% CI of IR

n (%)

IR

95% CI of IR

n (%)

IR

95% CI of IR

TEAEsa,b

5857 (85.0)

32.5

31.7, 33.3

1131 (80.7)

50.3

47.5, 53.3

798 (85.6)

38.0

35.5, 40.8

 Mild

1799 (26.1)

10.0

9.5, 10.5

461 (32.9)

20.5

18.7, 22.5

276 (29.6)

13.2

11.7, 14.8

 Moderate

3025 (43.9)

16.8

16.2, 17.4

556 (39.7)

24.7

22.8, 26.9

419 (45.0)

20.0

18.2, 22.0

 Severe

1032 (15.0)

5.7

5.4, 6.1

114 (8.1)

5.1

4.2, 6.1

103 (11.1)

4.9

4.0, 6.0

Most Common TEAEsn

 Nasopharyngitis

1592 (23.1)

8.8

8.4, 9.3

202 (14.4)

9.0

7.8, 10.3

176 (18.9)

8.4

7.2, 9.7

 Upper respiratory tract infection

1114 (16.2)

6.2

5.8, 6.6

186 (13.3)

8.3

7.2, 9.6

122 (13.1)

5.8

4.9, 6.9

 Injection site reaction

698 (10.1)

3.9

3.6, 4.2

156 (11.1)

6.9

5.9, 8.1

93 (10.0)

4.4

3.6, 5.4

 Arthralgia

642 (9.3)

3.6

3.3, 3.8

34 (2.4)

1.5

1.1, 2,1

66 (7.1)

3.1

2.5, 4.0

 Headache

541 (7.8)

3.0

2.8, 3.3

56 (4.0)

2.5

1.9, 3.2

41 (4.4)

2.0

1.4, 2.7

 Back pain

447 (6.5)

2.5

2.3, 2.7

65 (4.6)

2.9

2.3, 3.7

50 (5.4)

2.4

1.8, 3.1

 Hypertension

433 (6.3)

2.4

2.2, 2.6

64 (4.6)

2.8

2.2, 3.6

46 (4.9)

2.2

1.6, 2.9

 Bronchitis

410 (5.9)

2.3

2.1, 2.5

91 (6.5)

4.0

3.3, 5.0

72 (7.7)

3.4

2.7, 4.3

 Diarrhoea

387 (5.6)

2.1

1.9, 2.4

61 (4.4)

2.7

2.1, 3.5

60 (6.4)

2.9

2.2, 3.7

 Sinusitis

384 (5.6) 364

2.1

1.9, 2.4

77 (5.5)

3.4

2.7, 4.3

39 (4.2)

1.9

1.4, 2.5

 Urinary Tract Infection

(5.3)

2.0

1.8, 2.2

69 (4.9)

3.1

2.4, 3.9

45 (4.8)

2.1

1.6, 2.9

 Pharyngitis

307 (4.5)

1.7

1.5, 1.9

54 (3.9)

2.4

1.8, 3.1

61 (6.5)

2.9

2.3, 3.7

 Injection site erythema

203 (2.9)

1.1

1.0, 1.3

60 (4.3)

2.7

2.1, 3.4

33 (3.5)

1.6

1.1, 2.2

 Cough

334 (4.8)

1.9

1.7, 2.1

48 (3.4)

2.1

1.6, 2.8

17 (1.8)

0.8

0.5, 1.3

SAEso

969 (14.1)

5.4

5.0, 5.7

134 (9.6)

6.0

5.0, 7.1

101 (10.8)

4.8

4.0, 5.9

Deaths

36 (0.5)

0.2

0.1, 0.3

6 (0.4)

0.3

0.1, 0.6

3 (0.3)

0.1

0.0, 0.4

AE leading to discontinuation (including death)

519 (7.5)

2.9

2.6, 3.1

115 (8.2)

5.1

4.3, 6.1

66 (7.1)

3.1

2.5, 4.0

Selected AEs of interest

 Infections

4307 (62.5)

23.9

23.2, 24.6

759 (54.2)

33.8

31.4, 36.3

540 (57.9)

25.7

23.7, 28.0

 Serious Infections

231 (3.4)

1.3

1.1, 1.5

28 (2.0)

1.2

0.9, 1.8

23 (2.5)

1.1

0.7, 1.6

 Opportunistic Infections

536 (7.8)

3.0

2.7, 3.2

86 (6.1)

3.8

3.1, 4.7

28 (3.0)

1.3

0.9, 1.9

 Oral candidiasis

144 (2.1)c

0.8

0.7, 0.9

16 (1.1)d

0.7

0.4, 1.2

5 (0.5)e

0.2

0.1, 0.6

 Oral fungal infectionf

11 (0.2)

0.1

0.0, 0.1

6 (0.4)

0.3

0.1, 0.6

3 (0.3)

0.1

0.0, 0.4

 Esophageal candidiasis

14 (0.2)

0.1

0.0, 0.1

2 (0.1)

0.1

0.0, 0.4

4 (0.4)

0.2

0.1, 0.5

 Herpes zoster

120 (1.7)

0.7

0.6, 0.8

16 (1.1)

0.7

0.4, 1.2

12 (1.3)

0.6

0.3, 1.0

 Candida Infections

337 (4.9)

1.9

1.7, 2.1

45 (3.2)

2.0

1.5, 2.7

26 (2.8)

1.2

0.8, 1.8

 Oral Candidag

160 (2.3)

0.9

0.8, 1.0

22 (1.6)

1.0

0.6, 1.5

8 (0.9)

0.4

0.2, 0.8

 Vulvovaginal Candidah

97 (4.4)

1.7

1.4, 2.1

13 (1.8)

1.1

0.7, 2.0

7 (2.5)

1.2

0.6, 2.5

 Skin Candida

52 (0.8)

0.3

0.2, 0.4

5 (0.4)

0.2

0.1, 0.5

2 (0.2)

0.1

0.0, 0.4

 Esophageal candidiasis

16 (0.2)

0.1

0.1, 0.1

2 (0.1)

0.1

0.0, 0.4

5 (0.5)

0.2

0.1, 0.6

 Latent Tuberculosis

106 (1.5)

0.6

0.5, 0.7

35 (2.5)

1.6

1.1, 2.2

2 (0.2)

0.1

0.0, 0.4

 Inflammatory bowel diseasei

26 (0.4)

0.1

0.1, 0.2

3 (0.2)

0.1

0.0, 0.4

17 (1.8)

0.8

0.5, 1.3

 Crohn’s disease

10 (0.1)

0.1

0.0, 0.1

2 (0.1)

0.1

0.0, 0.4

7 (0.8)

0.3

0.2, 0.7

 Ulcerative colitis

16 (0.2)

0.1

0.1, 0.1

1 (0.1)

0.0

0.0, 0.3

10 (1.1)

0.5

0.3, 0.9

 Injection site reactionsP

1056 (15.3)

5.9

5.5, 6.2

260 (18.6)

11.6

10.2, 13.1

156 (16.7)

7.4

6.4, 8.7

 Allergic reactions/hypersensitivities

1001 (14.5)

5.6

5.2, 5.9

102 (7.3)

4.5

3.7, 5.5

88 (9.4)

4.2

3.4, 5.2

 Malignancies

141 (2.0)

0.8

0.7, 0.9

15 (1.1)

0.7

0.4, 1.1

9 (1.0)

0.4

0.2, 0.8

 NMSC

55 (0.8)

0.3

0.2, 0.4

9 (0.6)

0.4

0.2, 0.8

0 (0.0)

0.0

0.0, 0.4

 Malignancies excluding NMSC

88 (1.3)

0.5

0.4, 0 .6

7 (0.5)

0.3

0.1, 0.7

9 (1.0)

0.4

0.2, 0.8

 Asthma

49 (0.7)

0.3

0.2, 0.4

10 (0.7)

0.4

0.2, 0.8

5 (0.5)

0.2

0.1, 0.6

 Depression and suicide/self-injuryj

215 (3.1)

1.2

1.0, 1.4

37 (2.6)

1.6

1.2, 2.3

19 (2.0)

0.9

0.6, 1.4

 MACEk

91 (1.3)

0.5

0.4, 0.6

12 (0.9)

0.5

0.3, 0.9

6 (0.6)

0.3

0.1, 0.6

 Cytopenial

171 (2.5)

0.9

0.8, 1.1

56 (4.0)

2.5

1.9, 3.2

28 (3.0)

1.3

0.9, 1.9

 Iridocyclitism

2 (0.0)

0.0

0.0,0.0

0 (0)

0

0.0, 0.0

58 (6.2)

2.8

2.1, 3.6

  1. Abbreviations: axSpA Axial spondyloarthritis, CI Confidence interval, IR Incidence rate, IXE Ixekizumab, MACE Major adverse cerebro-cardiovascular event, MedDRA Medical Dictionary for Regulatory Activities, N Number of patients in the analysis population; n, number of patients in each category, NMSC Non-melanoma skin cancer, PsA Psoriatic arthritis, PsO Psoriasis, SAE Serious adverse event, SMQ Standardized MedDRA Queries TEAE treatment-emergent adverse event
  2. aPatients with multiple occurrences of the same event are counted under the highest severity
  3. b1 missing case of severity in the PsO cohort
  4. cThe data include 3 cases considered severe, 65 cases considered moderate, and 76 cases considered mild
  5. dData included 3 cases considered moderate and 13 cases considered mild
  6. eData included 2 cases considered moderate and 3 cases considered mild
  7. fAs reported by investigator
  8. gOral Candida infection includes oral candidiasis, oral fungal infection and oropharyngeal candidiasis
  9. hPsO Cohort: Denominator adjusted because gender-specific event for females; N = 2196, PY = 5580.5. PsA Cohort: Denominator adjusted due to gender-specific event for females; N = 722, PY = 1142.2 (pooled IXE). axSpA Cohort: Denominator adjusted because gender-specific event for females; N = 282, PY = 592.8 (pooled IXE)
  10. iData represent adjudicated cases. For the PsO cohort, the data represents cases classified as “definite” and “probable” per external adjudication. IR was calculated as the total of “definite” and “probable” cases /total patient-years, then multiplied by 100. There were 5 cases of adjudicated IBD that were not considered TEAEs. Total adjudicated IBD n = 31 (0.4%, IR of 0.2 per 100 PY). 5 additional cases confirmed by adjudication occurred either on the safety follow-up period (n = 3) or on the placebo maintenance period after IXE treatment (n = 2). 3 patients with PsO had a history of IBD. For the axSpA cohort, 12 cases de novo, 5 patients had a history of IBD and experienced a flare during the study period. 1 additional case of IBD was reported in the safety follow-up
  11. jBroad, according to Standardized MedDRA Queries (SMQ) or sub-SMQ classification
  12. kadjudicated cases
  13. lSMQ classification
  14. m4 cases of uveitis were reported among patients in the PsO cohort (0.1%, IR 0.0 per 100 PY), 8 cases of uveitis were reported among patients in the axSpA cohort (0.9%, IR 0.4 per 100 PY). All studies were conducted using the original, citrate-containing formulation of IXE. AE terms were derived from MedDRA version 24.1 for PsO and axSpA-related studies, version 23.1 for PsA-related studies
  15. nMost common TEAEs are defined as those with an IR > 2.0
  16. oData collection for the clinical trial database does not specify when events became serious and therefore the numbers shown may represent more serious events than what actually occurred during the treatment period
  17. PPreferred MedDRA term. All studies included in these analyses used the original, citrate-containing IXE formulation. axSpA cohort includes patients with AS and nr-axSpA
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Arthritis Research & Therapy

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