US-MULT-230356
For adult patients with moderate to severe ulcerative colitis (UC)
*Clinical remission was defined as a total Mayo score of ≤2 with no subscore >1.1,2
†Clinical response is defined as a decrease in total Mayo score of ≥3 points from baseline and a decrease in total Mayo score of ≥30% from baseline and a decrease in the rectal bleeding score of ≥1 or an absolute rectal bleeding subscore of 0 or 1.2
ULTRA I Study Design Intro: 8-week, randomized, double-blind, placebo-controlled study in 390 anti-TNF-naïve adult patients with inadequate response to concurrent or prior immunosuppressant therapy and evaluated 3 treatment arms. Primary endpoint: percentage of patients achieving clinical remission at Week 8.1,2
ULTRA II Study Design Intro: 52-week, randomized, double-blind, placebo-controlled study in 518* adult patients with inadequate response to concurrent or prior immunosuppressant therapy, as well as patients who lost response or were intolerant to anti-TNF agents.† Two treatment arms were evaluated (± concomitant therapy). Co-primary endpoints: percentage of patients achieving clinical remission at Weeks 8 and 52.1,3
*24 patients were not included in the efficacy analysis due to site noncompliance.
†Patients with prior exposure to HUMIRA were excluded from the study.
TNF=tumor necrosis factor
*Clinical remission was defined as a total Mayo score of ≤2 with no subscore >1.
EOW=every other week; TNF=tumor necrosis factor
Subgroup analyses are not powered or tested to demonstrate a statistically significant difference in treatment effect; no statistical inferences can be made due to the exploratory nature of the analysis.
Subgroup Analysis Methodology: The subgroup analysis is of the intention-to-treat study population of patients treated with HUMIRA EOW or placebo who achieved clinical remission (total Mayo score of ≤2 with no subscore >1) at Week 52, stratified by previous anti-TNF experience. Patients with missing data were classified as not achieving clinical response† or clinical remission.
*Clinical remission was defined as a total Mayo score of ≤2 with no subscore >1.
†Clinical response is defined as a decrease in total Mayo score of ≥3 points from baseline and a decrease in total Mayo score of ≥30% from baseline and a decrease in the rectal bleeding score of ≥1 or an absolute rectal bleeding subscore of 0 or 1.3
EOW=every other week; TNF=tumor necrosis factor
Subgroup analyses are not powered or tested to demonstrate a statistically significant difference in treatment effect; no statistical inferences can be made due to the exploratory nature of the analysis.
Subgroup Analysis Methodology: The subgroup analysis is of the intention-to-treat study population of patients treated with HUMIRA EOW or placebo who achieved mucosal healing (endoscopy subscore of 0 or 1) at Week 52, stratified by previous anti-TNF experience. Patients with missing data were classified as not achieving clinical response† or clinical remission.‡
*Mucosal healing is defined as an endoscopy subscore of 0 or 1 and did not include a histological analysis.
†Clinical remission was defined as a total Mayo score of ≤2 with no subscore >1.
‡Clinical response is defined as a decrease in total Mayo score of ≥3 points from baseline and a decrease in total Mayo score of ≥30% from baseline and a decrease in the rectal bleeding score of ≥1 or an absolute rectal bleeding subscore of 0 or 1.
EOW=every other week; TNF=tumor necrosis factor
*Clinical remission was defined as a total Mayo score of ≤2 with no subscore >1.
†Restricted to patients using corticosteroids at baseline.
EOW=every other week
Adverse reaction rates observed in clinical trials and OLE studies may not predict the rates observed in a broader patient population in clinical practice.
Rates (events per 100 PYs) of treatment-emergent adverse events (AEs)* of interest in 3 controlled and uncontrolled moderate to severe adult UC studies for✝:
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.
Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA.
The use of HUMIRA in UC beyond 1 year has not been evaluated in controlled clinical studies.
aData as of December 31, 2014.
bThree pooled controlled and uncontrolled studies.
cControl=placebo ± concomitant therapy.
*Treatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
†Excluding Japanese studies.
AE=adverse event; OLE=open-label extension; PYs=patient-years; TNF=tumor necrosis factor
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death, including active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease.
The use of HUMIRA in UC beyond 1 year has not been evaluated in controlled clinical studies.
aData as of December 31, 2014.
bThree pooled controlled and uncontrolled studies.
cControl=placebo ± concomitant therapy.
*Treatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
†Excluding Japanese studies.
AE=adverse event; OLE=open-label extension; PYs=patient-years; TNF=tumor necrosis factor
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.
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.
aExcluding non-melanoma skin cancer and lymphoma.
bData as of December 31, 2014.
cThree pooled controlled and uncontrolled studies.
dControl=placebo ± concomitant therapy.
*Treatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
†Excluding Japanese studies.
AE=adverse event; OLE=open-label extension; PYs=patient-years; TNF=tumor necrosis factor
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including HUMIRA.
The rate of lymphoma in controlled and uncontrolled clinical trials of HUMIRA was approximately 3-fold higher than expected in the general population.
Patients with chronic inflammatory diseases, particularly those with highly active disease, are at a higher risk for the development of lymphoma.
Study Design Intro: 52-week, randomized, double-blind, placebo-controlled study in 518* adult patients with inadequate response to concurrent or prior immunosuppressant therapy, as well as patients who lost response or were intolerant to anti-TNF agents.† Two treatment arms were evaluated (± concomitant therapy). Co‑Primary Endpoints: percentage of patients achieving clinical remission‡ at Week 8 and at Week 52.1,3
aData as of December 31, 2014.
bThree pooled controlled and uncontrolled studies.
cControl=placebo ± concomitant therapy.
*Treatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
†Excluding Japanese studies.
AE=adverse event; OLE=open-label extension; PYs=patient-years; TNF=tumor necrosis factor
Safety Considerations
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.
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.
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.
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.
| Without IMM n=1663 2160.87 PYs |
With IMM n=464 546.90 PYs |
Overall HUMIRA n=1984 2707.77 PYs |
Overall IMM n=2219 3364.54 PYs |
|
| Any AE | 19.2 | 25.4 | 20.5 | 14.4 |
| Serious AE | 8.6 | 9.0 | 8.6 | 5.8 |
| AE leading to registry discontinuation | 0.6 | 0.9 | 0.7 | 0.3 |
| Infection | 4.1 | 5.9 | 4.4 | 3.0 |
| Serious infection | 1.6 | 1.8 | 1.6 | 0.9 |
| Opportunistic infection (excl. oral candidiasis and tuberculosis) | <0.1 | 0 | <0.1 | 0 |
| Tuberculosis | <0.1 | 0.2 | <0.1 | <0.1 |
| Active | <0.1 | 0 | <0.1 | <0.1 |
| Latent | 0 | 0.2 | <0.1 | <0.1 |
| Any malignancy | 0.5 | 0.7 | 0.6 | 1.0 |
| Lymphoma | <0.1 | 0 | <0.1 | <0.1 |
| Non-melanoma skin cancer | 0.1 | 0.7 | 0.3 | 0.4 |
| AE leading to death | 0.2 | 0.4 | 0.2 | 0.1 |
Uncontrolled, observational, post-marketing registry7
Treatment-emergent AEs occurring from the first day in the registry up to 70 days after the last dose in the registry or up to the cut-off date are reported for all patients who received ≥1 registry dose of HUMIRA with or without concurrent immunomodulators (IMM) therapy.7
Enrollment will continue until the enrollment target of 8250 patients is reached.7
Study Design Intro: LEGACY is an ongoing, post‑marketing, 10-year, non-interventional, multinational registry assessing the long-term safety of HUMIRA or IMM as used in routine clinical practice in adults with moderately to severely active UC. All patients were dosed per their local label.7
IMM=immunomodulators; PYs=patient-years
Ulcerative Colitis (UC): HUMIRA is indicated for the treatment of moderately to severely active ulcerative colitis in adults and pediatric patients 5 years of age and older.
Limitations of Use:
The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to TNF blockers.
SERIOUS INFECTIONS
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.
MALIGNANCY
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.
HYPERSENSITIVITY
HEPATITIS B VIRUS REACTIVATION
NEUROLOGIC REACTIONS
HEMATOLOGIC REACTIONS
CONGESTIVE HEART FAILURE
AUTOIMMUNITY
IMMUNIZATIONS
ADVERSE REACTIONS
Please see Full Prescribing Information.
US-HUM-210183
References:
US-HUM-210672
US-HUM-210672
US-HUM-210672
US-HUM-210672
US-HUM-210672
HUMIRA has >90% preferred national commercial and Medicare Part D formulary coverage under the pharmacy benefit as of January 20231*
*Preferred means HUMIRA is on a preferred tier or otherwise has preferred status on the plan’s formulary.
Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursement policies.
Questions about access for your patients?
Learn more about how to help your patients access HUMIRA
1. Data on file, AbbVie Inc., January 2023.
US-HUM-220513
