ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the label:
- Infections [see Warnings and Precautions]
- Malignancies [see Warnings and Precautions]
- Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions]
Clinical Studies Experience
The safety data reflect exposure to STELARA™ in 2266 psoriasis subjects, including 1970 exposed for at least 6 months, 1285 exposed for at least one year, and 373 exposed for at least 18 months.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the STELARA™ groups than the placebo group during the placebo-controlled period of STUDY 1 and STUDY 2.
Table 1. Adverse reactions reported by ≥1% of subjects through Week 12 in STUDY 1 and STUDY 2
|
|
STELARA™ |
|
Placebo |
45 mg |
90 mg |
| Subjects treated |
665 |
664 |
666 |
| Nasopharyngitis |
51 (8%) |
56 (8%) |
49 (7%) |
| Upper respiratory tract infection |
30 (5%) |
36 (5%) |
28 (4%) |
| Headache |
23 (3%) |
33 (5%) |
32 (5%) |
| Fatigue |
14 (2%) |
18 (3%) |
17 (3%) |
| Diarrhea |
12 (2%) |
13 (2%) |
13 (2%) |
| Back pain |
8 (1%) |
9 (1%) |
14 (2%) |
| Dizziness |
8 (1%) |
8 (1%) |
14 (2%) |
| Pharyngolaryngeal pain |
7 (1%) |
9 (1%) |
12 (2%) |
| Pruritus |
9 (1%) |
10 (2%) |
9 (1%) |
| Injection site erythema |
3 (<1%) |
6 (1%) |
13 (2%) |
| Myalgia |
4 (1%) |
7 (1%) |
8 (1%) |
| Depression |
3 (<1%) |
8 (1%) |
4 (1%) |
Adverse drug reactions that occurred at rates less than 1% included: cellulitis and certain injection site reactions (pain, swelling, pruritus, induration, hemorrhage, bruising, and irritation). One case of RPLS occurred during clinical trials [see Warnings and Precautions].
Infections
In the placebo-controlled period of clinical studies of psoriasis subjects (average follow-up of 12.6 weeks for placebo-treated subjects and 13.4 weeks for STELARA ™ -treated subjects), 27% of STELARA™-treated subjects reported infections (1.39 per subject-year of follow-up) compared with 24% of placebo-treated subjects (1.21 per subject-year of follow-up). Serious infections occurred in 0.3% of STELARA™-treated subjects (0.01 per subject-year of follow-up) and in 0.4% of placebo-treated subjects (0.02 per subject-year of follow-up) [see Warnings and Precautions].
In the controlled and non-controlled portions of psoriasis clinical trials, 61% of STELARA™-treated subjects reported infections (1.24 per subject-year of follow-up). Serious infections were reported in 0.9% of subjects (0.01 per subject-year of follow-up).
Malignancies
In the controlled and non-controlled portions of psoriasis clinical trials, 0.4% of STELARA™-treated subjects reported malignancies excluding non-melanoma skin cancers (0.36 per 100 subject-years of follow-up). Non-melanoma skin cancer was reported in 0.8% of STELARA™-treated subjects (0.80 per 100 subject-years of follow-up) [see Warnings and Precautions].
Serious malignancies included breast, colon, head and neck, kidney, prostate, and thyroid cancers.
Immunogenicity
The presence of ustekinumab in the serum can interfere with the detection of anti-ustekinumab antibodies resulting in inconclusive results due to assay interference. In STUDIES 1 and 2, antibody testing was done at time points when ustekinumab may have been present in the serum. Table 2 summarizes the antibody results from STUDIES 1 and 2. In STUDY 1 the last ustekinumab injection was between Weeks 28 and 48 and the last test for anti-ustekinumab antibodies was at Week 52. In STUDY 2 the last ustekinumab injection was at Week 16 and the last test for anti-ustekinumab antibodies was at Week 24.
Table 2
| Antibody Results |
STUDY 1
(N=743) |
STUDY 2
(N=1198) |
| Positive |
38 (5%) |
33 (3%) |
| Negative |
351 (47%) |
90 (8%) |
| Inconclusive |
354 (48%) |
1075 (90%) |
The data reflect the percentage of subjects whose test results were positive for antibodies to ustekinumab in a bridging immunoassay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to ustekinumab with the incidence of antibodies to other products may be misleading.
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