c
(N=415)
Percent of Patients Percent of Patients
Infectiond (total) 39 50 86 81
Upper Respiratory
Infectionse 30 38 70 65
Non-upper
Respiratory 15 21 59 54
Infections
Injection Site
Reactions 11 37 18 43
Diarrhea 9 8 16 16
Rash 2 3 19 13
Pruritus 1 2 5 5
Pyrexia - 3 4 2
Urticaria 1 - 4 2
Hypersensitivity - - 1 1
a Includes data from the 6-month study in which patients received concurrent MTX therapy in both arms.
b Study duration of 2 years.
c Any dose.
d Includes bacterial, viral and fungal infections.
e Most frequent Upper Respiratory Infections were upper respiratory tract infection, sinusitis and influenza.
In placebo-controlled adult PsO trials, the percentages of patients reporting adverse reactions in the 50 mg twice aweek dose group were similar to those observed in the 25 mg twice a week dose group or placebo group.
Table 4 summarizes adverse reactions reported in adult PsO patients from Studies I and II.
Table 4. Percent of Adult PsO Patients Experiencing Adverse Reactions
in Placebo-Controlled Portions of Clinical Trials (Studies I & II)
Reaction
Placebo
(N=359)
Etanercepta
(N=876)
Percent Patients
Infectionb (total)
Non-upper Respiratory Infections
Upper Respiratory Infectionsc
Injection Site Reactions
Diarrhea
Rash
Pruritus
Urticaria
Hypersensitivity
Pyrexia
28
14
17
6
2
1
2
-
-
1
27
12
17
15
3
1
1
1
1
-
a Includes 25 mg subcutaneous (SC) once weekly (QW), 25 mg SC twice weekly (BIW), 50 mg SC QW, and 50 mg SCBIW doses.
b Includes bacterial, viral and fungal infections.
c Most frequent Upper Respiratory Infections were upper respiratory tract infection, nasopharyngitis and sinusitis.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highlydependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (includingneutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology,sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons,comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in otherstudies or to other etanercept products may be misleading.
Immunogenicity
Patients with RA, PsA, AS or PsO were tested at multiple time points for antibodies to etanercept. Antibodies to the TNF receptor portion or other protein components of the etanercept drug product were detected at least once in sera ofapproximately 6% of adult patients with RA, PsA, AS or PsO. These antibodies were all non-neutralizing.
Resultsfrom JIA patients were similar to those seen in adult RA patients treated with etanercept.
In adult PsO studies that eva luated the exposure of etanercept for up to 120 weeks, the percentage of patients testingpositive at the assessed time points of 24, 48, 72 and 96 weeks ranged from 3.6%-8.7% and were all non-neutralizing.
The percentage of patients testing positive increased with an increase in the duration of study; however, the clinicalsignificance of this finding is unknown. No apparent correlation of antibody development to clinical response oradverse events was observed. The immunogenicity data of etanercept beyond 120 weeks of exposure are unkn |
