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.
Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
ATLAS was a 24-week, multicenter, randomized, double-blind, placebo-controlled study of 315 patients with active AS who had an inadequate response or intolerance to 1 or more nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were randomized to receive HUMIRA 40 mg every other week (EOW), (n=208) or placebo (n=107).
The co-primary endpoints were 1) ASAS 20 response (≥20% improvement according to the Assessment in Ankylosing Spondylitis International Working Group criteria) at Week 12 for HUMIRA compared to placebo EOW; and 2) change in modified Stoke AS Spine Score (mSASSS) from baseline to Week 104 for the HUMIRA cohort (n=307) compared to the Outcome in AS International Study (OASIS) cohort, a historical control cohort of TNF-antagonist naïve patients (n=169).2,3 Select secondary endpoints were ASAS20 at Week 24, MASES, and ASQoL.2
At Week 24, patients completing the placebo-controlled, double-blind portion of the trial were eligible for enrollment in the open-label extension (OLE).4
EOW=every other week.
aPatients who did not achieve an ASAS20 response at Weeks 12, 16, or 20 were considered for open-label HUMIRA.4
Patients who did not achieve an ASAS20 response could switch to open-label HUMIRA (“early escape” protocol) at Weeks 12, 16, and 20; 69.2% (74/107) of placebo patients and 38.9% (81/208) of HUMIRA patients entered the early escape protocol.
Active AS was defined as fulfillment of at least 2 of the following: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4; total back pain score ≥4 (VAS 0-10 cm); morning stiffness lasting ≥1 hour.2
ASAS=Assessment in Ankylosing Spondylitis International Working Group; BASFI=Bath Ankylosing Spondylitis Functional Index; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; MASES=Maastricht Ankylosing Spondylitis Enthesitis Score.
BASFI=Bath Ankylosing Spondylitis Functional Index.
aLast observation carried forward (LOCF) analysis of intent-to-treat population. If a patient received early-escape open-label adalimumab prior to Week 24, the last observation prior to early-escape open-label adalimumab was carried forward.
aMaastricht Ankylosing Spondylitis Enthesitis Score (MASES). Evaluates 13 tendon insertion points for pain
(total score, 0-13).
dLast observation carried forward (LOCF) analysis of the intent-to-treat population.
aAnkylosing Spondylitis Quality of Life (ASQoL). Comprised of 18 statements to be filled in by the patient. Each statement on the ASQoL is given a score of "1" or "0." All item scores are summed to give a total score or index. Scores range from 0 (good quality of life) to 18 (poor quality of life).
aObserved analysis by duration of exposure to HUMIRA 40 mg EOW using last observation prior to the first dose of adalimumab at baseline.
aThe majority of patients treated with placebo for the first 24 weeks of the ATLAS study did not have 2
years of exposure to adalimumab at the time of the analysis.
bAll values are the mean (SD). For observed and last observation carried forward (LOCF) analyses, the baseline value is the last observation before the first dose of adalimumab.
As with any long-term open-label extension, there are several limitations with the OLE portion of this study. For example, there is the potential for enrichment of long-term data in the remaining patient population, as those who remain in the study generally fare better than those who discontinue.
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
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. van der Heijde D, Kivitz A, Schiff MH, et al; for ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136-2146. 3. van der Heijde D, Salonen D, Weissman B, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11(4):R127. 4. van der Heijde D, Schiff MH, Sieper J, et al; for ATLAS Study Group. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis. 2009;68(6):922-929. 5. van der Heijde DM, Revicki DA, Gooch KL, et al. Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis. Arthritis Res Ther. 2009;11(4):R124. 6. Data on File ABBVRTI62990.