For adult patients with moderate to severe rheumatoid arthritis (RA).
Model not an actual patient.
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
aBoth patients were female and Caucasian5:
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
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
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
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
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
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
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
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
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.
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
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
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
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
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
DE019—Adult patients with established moderate to severe RA who had an inadequate response to MTX1,3
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
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.
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
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
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
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.
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
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
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
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
PREMIER—Adult patients with early moderate to severe RA (less than 3 years' duration) who were MTX-naïve1,2
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
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.
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.
Rheumatoid Arthritis: 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: 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: 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: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Crohn’s Disease: HUMIRA is indicated for the treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older.
Ulcerative Colitis: 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.
Plaque Psoriasis: 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: 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.
US-HUM-210183
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.