For adult patients with moderate to severe rheumatoid arthritis (RA).
EFFICACY
HUMIRA® (adalimumab) + MTX:
Proven to help prevent further joint
damage and improve
physical function1
Model not an actual patient.
Clinical trials overview
PREMIER study design intro: 2-year, double-blind, active comparator-controlled study of adult patients with early moderate to severe RA (<3 years' duration) and who were MTX-naïve. 799 patients were randomized to receive HUMIRA 40 mg EOW + MTX weekly (n=268), HUMIRA 40 mg EOW (n=274), or MTX weekly (n=257). Co‑primary endpoints were ACR50 response and change from baseline in mTSS at Week 52.1,2
DE019 study design intro: 1-year, double-blind, placebo-controlled study of adult patients with established moderate to severe RA who had an inadequate response to MTX. 619 patients were randomized to receive HUMIRA 40 mg EOW + MTX (n=207), HUMIRA 20 mg weekly + MTX (n=212), or placebo + MTX (n=200). The primary endpoints were ACR20 response at Week 24, mean change from baseline in mTSS at Week 52, and mean change from baseline in HAQ-DI physical function score at Week 52.1,3
ARMADA study design intro: 24-week, double-blind, placebo-controlled study of adult patients who had active moderate to severe RA despite treatment with MTX ≥6 months. 271 patients were randomized to receive HUMIRA 80 mg EOW + MTX (n=73), HUMIRA 40 mg EOW (n=67), HUMIRA 20 mg EOW + MTX (n=69) or placebo + MTX (n=62). The primary endpoint was the ACR20 response at Week 24.1,4
ACR=American College of Rheumatology; EOW=every other week; HAQ DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate
Radiographic progression
Radiographs of study patients enrolled in PREMIER5,a
aBoth patients were female and Caucasian5:
- HUMIRA + MTX patient: 48 years old
- MTX patient: 44 years old
JE=joint erosion; JSN=joint space narrowing; mTSS=modified total Sharp score; MTX=methotrexate
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
Sustained greater inhibition of joint damage through
2 years vs MTX alone1,2
Mean change from baseline mTSS at
Year 1 and 21,2
aAnalysis of the intent-to-treat (ITT) study population. Values for missing data were imputed by a predefined linear progression method.
Sustained greater inhibition of joint damage
through 2 years vs MTX alone1,2
Components of mTSS2,a
aChange in mTSS=Change in JE + Change in JSN2
EOW=every other week; JE=joint erosion; JSN=joint space narrowing; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
Up to 10 years of radiographic data: Mean change
in mTSS in completer cohort6-8
aAll data were observed. No imputation was employed. Clinical efficacy was evaluated in patients who entered the PREMIER OLE by duration of exposure to HUMIRA
OLE Limitations
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.
PREMIER OLE study design intro: 497 patients from the PREMIER trial entered the OLE at Year 2. All patients received HUMIRA 40 mg EOW. Physician could add MTX at any time based on clinical judgment.6
ACR=American College of Rheumatology; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open‑label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
Sustained greater inhibition of joint damage
through 52 weeks vs MTX alone3,9
Mean change from baseline mTSS at
Weeks 24 and 523,9
aExtrapolated analysis of the intent-to-treat (ITT) population. Missing Sharp score values were imputed by linear extrapolation from baseline and Week 24 to Week 52.
EOW=every other week; JE=joint erosion; JSN=joint space narrowing; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
Joint erosion and joint space narrowing,
components of mTSS, at Week 523,a
aChange in mTSS = Change in JE + Change in JSN3
bLast observation carried forward (LOCF) analysis of the intent‑to‑treat (ITT) study population.
EOW=every other week; JE=joint erosion; JSN=joint space narrowing; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
Up to 10 years of radiographic data:
Mean change in mTSS in
completer cohort10,11
aAll data were observed. No imputation was employed. Only patients with available X-rays at baseline and Year 10 who received HUMIRA 40 mg EOW + MTX during the original RCT and through 10 years of treatment were included in this analysis. Radiographs collected at baseline and Year 1 were reevaluated along with those from OLE as one “read” by blinded assessors. Radiographs were scored by two independent readers blinded to subject, side, treatment, and chronological order of images. Scores were averaged to obtain the mTSS for each set of X‑rays.
55% of patients originally treated with HUMIRA 40 mg EOW + MTX were evaluated radiographically at 5 years. 50% of these patients showed no progression of structural damage defined by a change in mTSS of 0 or less. The overall mean change in mTSS at 5 years for patients originally treated with HUMIRA + MTX was 0.8.1,12
OLE Limitations
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.
DE019 OLE study design intro: 457 patients from the DE019 trial enrolled in the OLE at Year 1. All patients received HUMIRA 40 mg EOW + MTX.8
EOW=every other week; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
Signs & symptoms
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
Significantly greater ACR20/50/70 response rates
at Weeks 52 and 104 with HUMIRA® (adalimumab) + MTX1,2
aThe analysis is of the intent-to-treat (ITT) population using nonresponder imputation (NRI) methodology. Patients who withdrew or had missing values were considered nonresponders.
Secondary endpoint: ∼2x more patients achieved major clinical response (defined as achieving ACR70 and maintaining it for ≥6 months) with HUMIRA + MTX at Year 2 vs MTX alone (49% vs 27%, respectively;
P<0.001)2
ACR=American College of Rheumatology; EOW=every other week; OLE=open-label extension; RCT=randomized controlled trial
Significantly greater ACR20/50/70 response rates
at Weeks 52 and 104 with HUMIRA® (adalimumab) + MTX1,2
bThe analysis is of the intent-to-treat (ITT) population using nonresponder imputation (NRI) methodology. Patients who withdrew or had missing values were considered nonresponders.
Secondary endpoint: ∼2x more patients achieved major clinical response (defined as achieving ACR70 and maintaining it for ≥6 months) with HUMIRA + MTX at Year 2 vs MTX alone (49% vs 27%, respectively; P<0.001)2
ACR=American College of Rheumatology; EOW=every other week; OLE=open-label extension; RCT=randomized controlled trial
Significantly greater ACR20/50/70 response rates
at Weeks 52 and 104 with HUMIRA® (adalimumab) + MTX1,2
aThe analysis is of the intent-to-treat (ITT) population using nonresponder imputation (NRI) methodology. Patients who withdrew or had missing values were considered nonresponders.
Secondary endpoint: ∼2x more patients achieved major clinical response (defined as achieving ACR70 and maintaining it for ≥6 months) with HUMIRA + MTX at Year 2 vs MTX alone (49% vs 27%, respectively;
P<0.001)2
ACR=American College of Rheumatology; EOW=every other week; OLE=open-label extension; RCT=randomized controlled trial
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
PREMIER ACR OLE at Year 107,14
aAll data were observed. No imputation was employed. Clinical efficacy was evaluated in patients who entered the PREMIER OLE by duration of exposure to HUMIRA.
OLE Limitations
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.
PREMIER OLE study design intro: 497 patients from the PREMIER trial entered the OLE at Year 2. All patients received HUMIRA 40 mg EOW. Physicians could add MTX at any time based on clinical judgment.6
ACR=American College of Rheumatology; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open‑label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
Significantly greater ACR20/50/70 response rates
at Week 24 that were maintained through Week 521,3
aNonresponder imputation (NRI) analysis of intent-to-treat (ITT) population. Patients who withdrew or received additional traditional DMARDs on or after Week 16 were considered nonresponders.
∼2x more HUMIRA + MTX patients demonstrated ACR20 response at first visit (Week 2) compared to patients taking placebo (26% vs 13%, respectively; P≤0.001)3
ACR=American College of Rheumatology; EOW=every other week; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA
who had an inadequate response to MTX1,3
DE019 OLE at Year 1015
aAll data were observed. No imputation was employed. Clinical efficacy was evaluated in patients who entered the DE019 OLE by duration of exposure to HUMIRA.12
OLE Limitations
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.
DE019 OLE study design intro: 457 patients from the DE019 trial enrolled in the OLE at Year 1. All patients received HUMIRA 40 mg EOW + MTX.10
ACR=American College of Rheumatology; EOW=every other week; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
ARMADA—Adult patients with active moderate to severe RA despite long-term treatment with MTX1,4
4.5x more patients achieved an ACR20 response
with HUMIRA® (adalimumab) + MTX vs placebo + MTX at Week 244
aLast observation carried forward (LOCF) analysis of the
intent-to-treat (ITT) population. Patients who did not complete the 24‑week study were considered nonresponders.
25.4% of patients treated with HUMIRA 40 mg EOW + MTX (n=67) achieved an ACR20 response vs 6.5% of patients treated with placebo + MTX (n=62) at the time of first visit (Week 1)4
ACR=American College of Rheumatology; EOW=every other week; MTX=methotrexate
Pain reduction
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
HUMIRA + MTX delivered reductions
in patients’ assessment of paina twice that of MTX3
Mean baseline VAS values were 55.9 ± 20.4 for HUMIRA 40 mg EOW + MTX and 56.3 ± 22.9 for placebo + MTX.
Mean absolute change at Week 24 values were -28.2 ± 25.8 for HUMIRA 40 mg EOW + MTX and -12.6 ± 26.1 for placebo + MTXc
Mean absolute change at Week 52 values were -29.4 ± 26.4 for HUMIRA 40 mg EOW + MTX and -11.2 ± 27.7 for placebo + MTXc
aPatients’ assessment of pain, measured by using 0-100 mm VAS (0=no pain and 100=severe pain).
cAll values are the mean ± SD based on the last observation carried forward to Week 24 or Week 52. A negative mean change indicates an improvement in that ACR criterion.
ACR=American College of Rheumatology; EOW=every other week; MTX=methotrexate; VAS=visual analog scale
OLE Data—Open-label extension (OLE) data from DE019
DE019: Long-term pain relief
In an observed 10‑year analysis, patients treated with HUMIRA + MTX experienced a
in their assessment of paina from baseline16,b
Mean baseline value was 52.62 ± 21.34 and mean absolute change from baseline was -31.28 ± 28.03.
Mean absolute change was -31.28 ± 28.03 and the mean baseline value was 52.62 ± 21.34.
aPatients' assessment of pain, measured by using 0-100 mm VAS (0=no pain and 100=severe pain).
bAll data were observed. No imputation was employed. Clinical efficacy was evaluated in patients who entered the DE019 OLE by duration of exposure to HUMIRA.
OLE Limitations
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.
DE019 OLE study design intro: 457 patients from the DE019 trial enrolled in the OLE at Year 1. All patients received HUMIRA 40 mg EOW + MTX.10
EOW=every other week; MTX=methotrexate; OLE=open‑label extension; VAS=visual analog scale
Physical function
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
Significantly improved physical function so that patients
were able to get back to their daily activities1,5,17
aAll data were observed. No imputation was employed.
Secondary endpoint: Significantly greater improvement from baseline in HAQ-DI with HUMIRA + MTX vs MTX alone at Years 1 and 2: -1.1 vs -0.8 (P<0.001) and -1.0 vs -0.9 (P<0.05), respectively17
EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
10 years of physical function data: Mean HAQ‑DI7,18
aAll data were observed. No imputation was employed. Clinical efficacy was evaluated in patients who entered the PREMIER OLE by duration of exposure to HUMIRA.
OLE Limitations
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.
PREMIER OLE study design intro: 497 patients from the PREMIER trial entered the OLE at Year 2. All patients received HUMIRA 40 mg EOW. Physician could add MTX at any time based on clinical judgment.6
EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate; OLE=open‑label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
Significantly improved physical function so that patients
were able to get back to their daily activities1,3
aLast observation carried forward (LOCF) analysis of the intent-to-treat (ITT) study population
2x greater improvement in HAQ-DI in HUMIRA + MTX-treated patients vs placebo + MTX patients at Year 1: -0.59 vs -0.25 (P≤0.001)3
EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; MTX=methotrexate; OLE=open-label extension; RCT=randomized controlled trial
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
10 years of physical function data:
Mean change in HAQ-DI scores through 10 years10,11
aAll data were observed. No imputation was employed. Physical function was evaluated in patients who entered the DE019 OLE by duration of exposure to HUMIRA.
The mean change from baseline in HAQ-DI at Year 10 was -0.62 (n=149).11
OLE Limitations
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.
DE019 OLE study design intro: 457 patients from the DE019 trial enrolled in the OLE at Year 1. All patients received HUMIRA 40 mg EOW + MTX.10
EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; MTX=methotrexate; OLE=open-label extension
Additional measures
Clinical remission* (DAS28 <2.6)
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
~2x more patients achieved DAS28 remission
with HUMIRA + MTX vs MTX alone2,a
Response rates sustained at Year 2
Percent of patients meeting response criterion DAS28 <2.6
aClinical remission at Year 1 was a secondary endpoint and was defined as DAS28 <2.6. Disease activity score (DAS) is a composite index that includes variables such as the number of tender and swollen joints and either erythrocyte sedimentation rate or C-reactive protein (CRP), and may include the patient's assessment of disease activity.
*Clinical remission does not mean drug‑free remission or complete absence of disease activity.
ACR=American College of Rheumatology; DAS=disease activity score; EOW=every other week; mTSS=modified total Sharp score; MTX=methotrexate; RCT=randomized controlled trial
Indication1
Rheumatoid Arthritis (RA): HUMIRA is indicated, alone or in combination with methotrexate or other non‑biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
IMPORTANT SAFETY INFORMATION1
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:
- Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti‑fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
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.
- Do not start HUMIRA during an active infection, including localized infections.
- Patients older than 65 years, patients with co‑morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
- If an infection develops, monitor carefully and initiate appropriate therapy.
- Drug interactions with biologic products: A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of HUMIRA with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.
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.
- Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in a patient with known malignancy.
- In clinical trials, more cases of malignancies were observed among HUMIRA-treated patients compared to control patients.
- Non‑melanoma skin cancer (NMSC) was reported during clinical trials for HUMIRA‑treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with HUMIRA.
- In HUMIRA clinical trials, there was an approximate 3‑fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.
- Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.
HYPERSENSITIVITY
- Anaphylaxis and angioneurotic edema have been reported following HUMIRA administration. If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.
HEPATITIS B VIRUS REACTIVATION
- Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
- Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
- Exercise caution in patients who are carriers of HBV and monitor them during and after HUMIRA treatment.
- Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming HUMIRA after HBV treatment.
NEUROLOGIC REACTIONS
- TNF blockers, including HUMIRA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain‑Barré syndrome.
- Exercise caution when considering HUMIRA for patients with these disorders; discontinuation of HUMIRA should be considered if any of these disorders develop.
- There is a known association between intermediate uveitis and central demyelinating disorders.
HEMATOLOGIC REACTIONS
- Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with HUMIRA.
- Consider stopping HUMIRA if significant hematologic abnormalities occur.
CONGESTIVE HEART FAILURE
- Worsening and new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have been observed with HUMIRA; exercise caution and monitor carefully.
AUTOIMMUNITY
- Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus‑like syndrome. Discontinue treatment if symptoms of a lupus‑like syndrome develop.
IMMUNIZATIONS
- Patients on HUMIRA should not receive live vaccines.
- Pediatric patients, if possible, should be brought up to date with all immunizations before initiating HUMIRA therapy.
- Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live‑attenuated vaccines in infants exposed to HUMIRA in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live‑attenuated) exposed infants.
ADVERSE REACTIONS
- The most common adverse reactions in HUMIRA clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.
INDICATIONS1
Rheumatoid Arthritis (RA): HUMIRA is indicated, alone or in combination with methotrexate or other non‑biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
Juvenile Idiopathic Arthritis (JIA): HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
Psoriatic Arthritis (PsA): HUMIRA is indicated, alone or in combination with non‑biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
Ankylosing Spondylitis (AS): HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Adult Crohn's Disease (CD): 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.
Pediatric Crohn's Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6‑mercaptopurine, or methotrexate.
Ulcerative Colitis (UC): HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6‑mercaptopurine. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti‑TNF agents.
Plaque Psoriasis (Ps): HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow‑up visits with a physician.
Hidradenitis Suppurativa (HS): HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Uveitis: HUMIRA is indicated for the treatment of non‑infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.
Please see full Prescribing Information.
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Breedveld FC, Weisman MH, Kavanaugh AF, et al, for the PREMIER Investigators. The PREMIER study: a multicenter, randomized, double‑blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26‑37. 3. Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo‑controlled, 52‑week trial. Arthritis Rheum. 2004;50(5):1400‑1411. 4. Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti‑tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48(1):35‑45. 5. Data on File. ABVRRTI62934. 6. Breedveld FC, Keystone EC, van der Heijde D, et al. Initial combination therapy with adalimumab plus methotrexate leads to better long‑term outcomes than with either monotherapy in patients with early rheumatoid arthritis: 8‑year results of an open‑label extension of a phase 3 trial. Poster presented at: 2011 ACR/ARHP Annual Scientific Meeting; November 5‑9, 2011; Chicago, IL. 7. Keystone EC, Breedveld FC, van der Heijde D, et al. Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10‑year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open‑label extension. J Rheumatol. 2014;41(1):5‑14. 8. Data on File. ABVRRTI66114. 9. Data on File. ABVRRTI61669. 10. Keystone EC, van der Heijde D, Kavanaugh A, et al. Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10‑year data in longstanding rheumatoid arthritis. J Rheumatol. 2013;40(9):1487‑1497.
11. Data on File. ABVRRTI62075.
12. Data on File. ABVRRTI61779.
13. Data on File. ABVRRTI63131.
14. Data on File. ABVRRTI66000.
15. Data on File. ABVRRTI63132.
16. Data on File. ABVRRTI67410.
17. Data on File. ABVRRTI62071.
18. Data on File. ABVRRTI62102.
PREMIER study design & baseline characteristics
Study design
PREMIER: A clinical study in patients with early moderate to severe RA (less than
3 years' duration) who were MTX‑naïve1,2,6
aIntent-to-treat (ITT) population2
bObserved data
cStable doses of concomitant nonsteroidal
anti-inflammatory drugs (NSAIDs) and corticosteroids were permitted. Patients taking MTX escalated to 20 mg weekly by Week 8 as needed/as tolerated.2,6
Co-primary endpoints2
- Percentage of patients who achieved ACR50 response at Year 1
- Mean change from baseline in mTSS for HUMIRA + MTX vs MTX alone at Year 1
Select secondary endpoints2
- ACR 20/70 responses at Year 1;
ACR 20/50/70 responses at Year 2 - Mean change from baseline in HAQ-DI at Year 1
- Mean change from baseline in mTSS at Year 2
- Major clinical response* at Year 2
- Clinical remission (defined by DAS28 <2.6) at Year 1
*Major clinical response defined as achieving an ACR70 response and maintaining it for ≥6 months
ACR=American College of Rheumatology; DAS=disease activity score; EOW=every other week; HAQ‑DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate
Baseline characteristics
Select patient characteristics at baseline in PREMIER2,a
PREMIER RCT baseline patient characteristics and disease duration were generally comparable between groups2
aAll values are mean
bP<0.05 among all treatment groups
cn=267 for HUMIRA + MTX; n=251 for MTX
DAS28=28-joint disease activity score; EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate; RCT=randomized controlled trial; TSS=total Sharp score
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Radiographic assessment: JE, JSN & mTSS scores3
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DE019 study design & baseline characteristics
Study design
DE019: A pivotal study in patients with established moderate to severe RA who had an inadequate response to MTX1,3,10
aIntent-to-treat (ITT) population3
bObserved data
cStable doses of concomitant nonsteroidal
anti-inflammatory drugs (NSAIDs) and corticosteroids were permitted.3
Primary endpoints3
- ACR20 response at Week 24
- Mean change from baseline in mTSS at Week 52
- Mean change from baseline in HAQ-DI at Week 52
Select secondary endpoints3
- ACR20 response at Week 52; ACR 50/70 response at Weeks 24 and 52
- Mean change from baseline in mTSS at Week 24
- Mean change from baseline in patient assessment of pain at Weeks 24 and 52
Select additional endpoints3
- Mean change from baseline in HAQ-DI at Year 1
ACR=American College of Rheumatology; EOW=every other week; HAQ-DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate
Baseline characteristics
Select patient characteristics at baseline in DE0193,a
DE019 RCT baseline characteristics were generally comparable between the HUMIRA group and control group3,13
aAll values are mean
bn=194 for HUMIRA + MTX; n=184 for placebo + MTX
HAQ-DI=Health Assessment Questionnaire Disability Index; mTSS=modified total Sharp score; MTX=methotrexate; TSS=total Sharp score; VAS=visual analog scale
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ACR response criteria and components
ACR Response Criteria
ACR response criteria incorporate physician and patient assessments, as well as acute inflammatory, pain, and physical function measures.3
ACR=American College of Rheumatology; CRP=C‑reactive protein; HAQ‑DI=Health Assessment Questionnaire Disability Index
ACR Components
Changes in ACR core component criteria at baseline and Week 24:3,*
*All values are the mean, except where indicated, based on the last observation carried forward to Week 24. A negative mean change indicates an improvement in that ACR criterion.
†p≤0.001 versus placebo
ACR=American College of Rheumatology; CRP=C‑reactive protein; EOW=every other week; HAQ‑DI=Health Assessment Questionnaire Disability Index; MTX=methotrexate
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ARMADA study design & baseline characteristics
Study design
ARMADA: A clinical trial in patients with active moderate to severe RA despite long‑term treatment with MTX1,4
aIntent-to-treat (ITT) population
bStable doses of concomitant nonsteroidal
anti-inflammatory drugs (NSAIDs) and corticosteroids were permitted.
Objectives
- Evaluate the clinical efficacy of HUMIRA in patients who were not responding adequately to MTX
- Evaluate the safety profile of HUMIRA + MTX
Patient population
- All patients had active RA despite treatment with MTX for at least 6 months. MTX dose must have been stable for at least 4 weeks prior to study entry
Primary endpoint
- ACR20 response at Week 24
Select secondary endpoints
- ACR50 and ACR70 responses
ACR=American College of Rheumatology; EOW=every other week; MTX=methotrexate
Baseline characteristics
Select patient characteristics at baseline4,a
aAll values are mean
EOW=every other week; DMARDs=disease-modifying antirheumatic drugs; HAQ-DI=Health Assessment Questionnaire Disability Index; MTX=methotrexate
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