The following topics are also discussed in detail in the Warnings and Precautions section:
Infusion-Related Reactions and Hypersensitivity Reactions [see Warnings and Precautions (5.1)] Infections [see Warnings and Precautions (5.2)] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3)] Liver Injury [see Warnings and Precautions (5.4)] 6.1 Clinical Trials ExperienceBecause 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.
The data described below reflect exposure to intrenous ENTYVIO in 3,326 patients and healthy volunteers in clinical trials, including 1,396 exposed for greater than one year, and 835 exposed for greater than two years.
Intrenous Infusion
The safety data described in Table 2 are derived from four controlled Phase 3 trials (UC Trials I and II and CD Trials I and III); data from adult patients receiving open-label intrenous ENTYVIO treatment at Weeks 0 and 2 (prior to entry into UC Trial II and CD Trial III) and from Weeks 6 to 52 (non-responders at Week 6 of UC Trial I and CD Trial I) are included [see Clinical Studies (14.1, 14.2)].
In these trials, 1,434 patients received ENTYVIO 300 mg intrenously for up to 52 weeks, and 297 patients received placebo for up to 52 weeks. Of these, 769 patients had ulcerative colitis and 962 patients had Crohn's disease. Patients were exposed for a mean duration of 259 days (UC Trials I and II) and 247 days (CD Trials I and III).
Adverse reactions were reported in 52% of patients treated with intrenous ENTYVIO and 45% of patients treated with placebo (UC Trials I and II: 49% with ENTYVIO and 37% with placebo; CD Trials I and III: 55% with ENTYVIO and 47% with placebo). Serious adverse reactions were reported in 7% of patients treated with intrenous ENTYVIO compared to 4% of patients treated with placebo (UC Trials I and II: 8% with ENTYVIO and 7% with placebo; CD Trials I and III: 12% with ENTYVIO and 9% with placebo).
The most common adverse reactions (reported by ≥3% of patients treated with intrenous ENTYVIO in the UC Trials I and II and CD Trials I and III combined group and ≥1% higher than in combined placebo group) were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities (Table 2).
Table 2. Adverse Reactions in ≥3% of Intrenous ENTYVIO-Treated Adult Patients and ≥1% Higher than in Placebo (UC Trials I and II* and CD Trials I and III*) Adverse ReactionENTYVIO IV† (N=1434)Placebo‡ (N=297) * Data from patients receiving open-label intrenous ENTYVIO treatment at Weeks 0 and 2 (prior to entry into UC Trial II and CD Trial III) and from Weeks 6 to 52 (non-responders at Week 6 of UC Trial I and CD Trial I) are included. † Patients who received ENTYVIO for up to 52 weeks. ‡ Patients who received placebo for up to 52 weeks. Nasopharyngitis13%7% Headache12%11% Arthralgia12%10% Nausea9%8% Pyrexia9%7% Upper respiratory tract infection7%6% Fatigue6%3% Cough5%3% Bronchitis4%3% Influenza4%2% Back pain4%3% Rash3%2% Pruritus3%1% Sinusitis3%1% Oropharyngeal pain3%1% Pain in extremities3%1%Safety data for patients (n=279) in UC Trials I and II and CD Trials I and III who received intrenous ENTYVIO at Weeks 0 and 2 and were then randomized to placebo at Week 6 for up to 52 weeks, and for patients (n=416) in CD Trial II, a 10-week Crohn's disease trial, are similar to those listed in Table 2.
Infusion-Related Reactions and Hypersensitivity Reactions
Serious infusion-related reactions and hypersensitivity reactions including anaphylaxis he been reported following intrenous ENTYVIO administration in clinical trials [see Warnings and Precautions (5.1)]. In UC Trials I and II and CD Trials I and III, one case of anaphylaxis [one out of 1,434 patients treated with intrenous ENTYVIO (0.07%)] was reported by a Crohn's disease patient during the second infusion (symptoms reported were dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) and was managed with discontinuation of infusion and treatment with antihistamine and intrenous hydrocortisone.
In UC Trials I and II and CD Trials I and III, 4% of patients treated with intrenous ENTYVIO and 3% of patients treated with placebo experienced an infusion-related reaction (IRR). The most frequently observed IRRs in the patients treated with intrenous ENTYVIO (reported more than twice) were nausea, headache, pruritus, dizziness, fatigue, infusion-related reaction, pyrexia, urticaria, and vomiting (each of these adverse reactions occurred in