Serious Infections: Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Malignancies: Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
Other Serious Adverse Reactions: Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.
Adult Crohn’s Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
In moderate to severe adult Crohn's disease (CD) patients with active disease despite conventional therapies
aClinical remission was defined as a Crohn's Disease Activity Index (CDAI) score <150 points
*Clinical response was defined as a reduction of ≥70 points from baseline CDAI score
The most common AEs (≥5% in the HUMIRA 160 mg/80 mg arm) reported in the CLASSIC-I clinical trial were any type of injection site reactions, infections, headache, nausea, pharyngitis, abdominal tenderness, flatulence, and nasopharyngitis.
CLASSIC-I was a 4-week, randomized, double-blind, placebo-controlled, multicenter study of 3 doses of HUMIRA vs control (placebo), all ± concomitant therapy in 299 adult patients with moderately to severely active Crohn’s disease naïve to anti-TNF therapy. Patients were randomized to receive HUMIRA 160 mg at Week 0 and 80 mg at Week 2, HUMIRA 80 mg at Week 0 and 40 mg at Week 2, HUMIRA 40 mg at Week 0 and 20 mg at Week 2 or control and followed through Week 4. Primary endpoint was the percentage of patients achieving induction of clinical remission in the 2 higher doses compared with control at Week 4.
aClinical remission was defined as a Crohn's Disease Activity Index (CDAI) score <150 points.
In CHARM, patients who responded to HUMIRA typically did so within 12 weeks from the first dose; therapy that continued beyond 12 weeks did not result in significantly more responses.1
*Clinical response was defined as a reduction of ≥70 points from baseline CDAI score
The most common AEs (≥5% in the HUMIRA 40 mg EOW arm with an incidence ≥ control) during the double-blind period of the CHARM clinical trial were infections, injection site reaction related AEs, nasopharyngitis, arthralgia, headache, abdominal pain, nausea, pyrexia, and influenza.
CHARM was a 56-week randomized, double-blind, placebo-controlled, multicenter study of 854 adult patients with moderately to severely active Crohn’s disease. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. At Week 4, patients who achieved clinical response (CR-70) were randomized to HUMIRA 40 mg EOW, HUMIRA 40 mg weekly, or control (placebo), all ± concomitant therapy. Co-primary endpoints were the percentage of patients achieving clinical remission at Weeks 26 and 56 for each HUMIRA group vs control in the 499 patients with CR-70 response at Week 4 after open-label induction therapy.
Risk of HSTCL1
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of fatal lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. The majority of cases were in adolescent and young adult males with inflammatory bowel disease who had received concomitant or prior treatment with azathioprine or 6-mercaptopurine.
a This subanalysis includes patients from the CHARM trial who were randomized responders, remained blinded on HUMIRA 40 mg EOW therapy for the duration of the trial, and entered the HUMIRA 40 mg EOW arm (n=75) of the OLE.
bClinical remission was defined as a Crohn’s Disease Activity Index (CDAI) score <150 points
EOW=every other week.
This subanalysis evaluated clinical remission to 108 weeks in adult patients who received HUMIRA 40 mg EOW during the open-label extension (OLE) of the CHARM study. Patients who dropped out of the trial or who were missing CDAI scores were not included in the analysis at each time point.
aThis subanalysis includes patients from the CHARM trial who were randomized responders, remained blinded on HUMIRA 40 mg EOW therapy for the duration of the trial, and entered the HUMIRA 40 mg EOW arm (n=75) of the OLE.
bA flare was defined as an increase in CDAI of ≥70 points and a CDAI above 220 when compared to Week 4 of the preceding randomized, controlled trial. Nonresponse was defined as a decrease of <70 points compared to the baseline visit in the preceding randomized, controlled trial.
aClinical remission was defined as a Crohn’s Disease Activity Index (CDAI) score <150 points
Response (CR-70) rates* in GAIN at Week4: HUMIRA 52% (n=82/159) vs control 34% (n=56/166); (P<0.01)1,6
*Clinical response was defined as a reduction of ≥70 points from baseline CDAI score
The most common AEs (≥5% in the HUMIRA arm) in the GAIN clinical trial were infections, any type of injection site reactions, abdominal pain, arthralgia, and headache.
GAIN was a 4-week, randomized, double-blind, placebo-controlled, multicenter study of 325 adult patients with moderately to severely active Crohn’s disease who had lost response to, or were intolerant to, infliximab. Patients were randomized to receive 160 mg at Week 0 and 80 mg at Week 2 or control (placebo), both ± concomitant therapy and followed through Week 4. Primary endpoint was the percentage of patients achieving induction of clinical remission in HUMIRA-treated patients vs control at Week 4.
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a serious infection or sepsis.
Reported infections include:
Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.
For full Prescribing Information, visit rxabbvie.com/pdf/humira.pdf
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References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323-333. 3. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007;132(1):52-65. 4. Data on File ABVRRTI61721. 5. Data on File ABVRRTI61726. 6. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn's disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829-838.
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