Rheumatology
Moderate to Severe
Rheumatoid Arthritis
Active
Psoriatic Arthritis
Active
Ankylosing Spondylitis
Moderate to Severe
Juvenile Idiopathic Arthritis
Non-Infectious
Intermediate, Posterior and Panuveitis
Dermatology
Moderate to Severe
Chronic Plaque Psoriasis
Active
Psoriatic Arthritis
Moderate to Severe
Hidradenitis Suppurativa
Gastroenterology
Moderate to Severe
Crohn's Disease
Moderate to Severe
Pediatric Crohn's Disease
Moderate to Severe
Ulcerative Colitis
Ophthalmology
Non-Infectious
Intermediate, Posterior and Panuveitis
For patients two years of age and older with moderate to severe polyarticular
juvenile idiopathic arthritis (JIA).
EFFICACY
Focused on symptom improvement and fewer patients experiencing disease flare in JIA1
Model not an actual patient.
Clinical trial overview
DE038 study design intro: Randomized, double‑blind, parallel‑group study of patients aged 4 to 17 years old with polyarticular JIA who were naïve to biologic DMARDs at baseline. The study consisted of a 16‑week, open‑label, lead‑in phase (Weeks 0 to 16), a 32‑week, double‑blind, withdrawal phase (Weeks 16 to 48), and an open‑label extension phase. Only patients who were ACR30 responders after the 16‑week, open‑label, lead‑in phase were randomized. In the double‑blind period, 133 patients were randomized to receive MTX + placebo (n=37), HUMIRA + MTX (n=38), HUMIRA (n=30), or placebo (n=28).* The primary endpoint was the percentage of patients not receiving MTX who had a disease flare† during the double‑blind phase of the study.1,2
*Body surface area (BSA) dose: HUMIRA 24 mg/m2 EOW up to a maximum dose of 40 mg EOW
†Disease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria
ACR=American College of Rheumatology; DMARDs=disease-modifying antirheumatic drugs; EOW=every other week; MTX=methotrexate
Disease flare
DE038—Patients 4 to 17 years of age with moderate to severe
polyarticular JIA who were naïve to biologic DMARDs1,2
Significantly fewer patients treated with
HUMIRA® (adalimumab) experienced disease flarea
vs placebo, during double‑blind phase (Weeks 16 to 48)1,2
aDisease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria
Significant reduction with HUMIRA compared to placebo for both monotherapy and in combination with MTX2
DE038—Patients 4 to 17 years of age with moderate to severe
polyarticular JIA who were naïve to biologic DMARDs1,2
Longer time to disease flarea in patients treated with
HUMIRA® (adalimumab) vs placebo, during double‑blind
phase (Weeks 16 to 48)3
aDisease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria
Significantly longer time with HUMIRA compared to placebo for both monotherapy and in combination with MTX.3
ACR=American College of Rheumatology; DMARDs=disease-modifying antirheumatic drugs; EOW=every other week; MTX=methotrexate
Signs & symptoms
DE038—Patients 4 to 17 years of age with moderate to severe
polyarticular JIA who were naïve to biologic DMARDs1,2
Greater ACR Pedi 70 response rates were sustained through 48 weeks with HUMIRA® (adalimumab) + MTX vs placebo + MTX, during double‑blind phase (Weeks 16 to 48)2,4
aNonresponder imputation (NRI) of the intent-to-treat population; a patient who flared according to protocol definition was declared a nonresponder regardless of the final pediatric ACR response.2
ACR Pedi 70 response is defined as improvements of at least 70% in at least 3 of the 6 core criteria and a worsening of ≥30% in no more than 1 core criterion.2
Secondary endpoint: Significantly greater response with HUMIRA + MTX vs placebo + MTX at Week 482
Significantly greater ACR Pedi 70 response rates
at Week 48 in patients treated with HUMIRA® (adalimumab) + MTX vs placebo + MTX2
aNonresponder imputation (NRI) of the intent-to-treat population; a patient who flared according to protocol definition was declared a nonresponder regardless of the final pediatric ACR response.2
ACR Pedi 30/50/70 responses are defined as improvements of at least 30%, 50%, and 70%, respectively, in at least 3 of the 6 core criteria and a worsening of ≥30% in no more than 1 core criterion.2
Secondary endpoint: Significantly greater response with HUMIRA + MTX vs placebo + MTX at Week 482
ACR=American College of Rheumatology; DMARDs=disease-modifying antirheumatic drugs; EOW=every other week; MTX=methotrexate
DE038—Patients 4 to 17 years of age with moderate to severe
polyarticular JIA who were naïve to biologic DMARDs1,2
ACR Pedi 30/50/70 response rates were maintained for up to 2 years in the OLE phase in patients treated with HUMIRA® (adalimumab)2,a
aPatient response during the first 104 weeks of the OLE phase regardless of whether HUMIRA was dosed according to body surface area (BSA) or body weight.2
bThe data are from the intent-to-treat population of 128 patients who entered the OLE phase of the study; for missing values, the last observation was carried forward.
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.
DE038 OLE study design intro: Patients who enrolled in the double-blind phase were eligible to receive open-label treatment with HUMIRA in an extension phase of the study.2
ACR=American College of Rheumatology; OLE=open-label extension
Indication1
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.
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. Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359(8):810‑820. 3. Data on File. ABVRRTI62135. 4. Data on File. ABVRRTI65388.
ACR Pedi criteria2
aMeasured using a 100-mm visual analog scale (0=no disease activity/“very well” overall well-being; 100=the most disease activity/“very poor” overall well‑being).
bDefined as swollen joints not caused by deformity or nonswollen joints with limited passive motion accompanied by pain and/or tenderness.
ACR=American College of Rheumatology
US-HUMR-190189
DE038 study design & baseline characteristics
Study design
DE038: A pivotal study in patients 4 to 17 years of age with moderate to severe polyarticular JIA1-3,a
aPatients remained on stable doses of NSAIDs and/or prednisone.
bBody surface area (BSA) dose: HUMIRA, 24 mg/m2 EOW up to a maximum dose of 40 mg EOW
cFixed dose (FD): HUMIRA 20 mg EOW if <30 kg; HUMIRA 40 mg EOW if ≥30 kg
Objective2
- To evaluate the efficacy and safety of HUMIRA monotherapy or HUMIRA + MTX in patients 4 to 17 years of age with polyarticular JIA who were naïve to biologic DMARDs at baseline
Patient population2
- All patients showed signs of active moderate or severe disease despite previous treatment with NSAIDs, analgesics, corticosteroids, or DMARDs, and were naïve to biologic DMARDs at baseline
- Only patients who were Pediatric ACR30 responders after the 16‑week, open‑label, lead‑in phase were randomized
Primary endpoint2
- Percentage of patients not receiving MTX who had a disease flare* during the double-blind phase of the study (Weeks 16 to 48)
Other selected endpoints2,3
- ACR Pedi 30, 50, 70 levels of response
- Median time to onset of disease flare during double‑blind phase
*Disease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria
ACR=American College of Rheumatology; DMARDs=disease-modifying antirheumatic drugs; EOW=every other week; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs
Baseline characteristics
Select baseline demographics and clinical characteristics in DE0382: Open-label lead‑in phasea
aAll values are means except values for C‑reactive protein, which are medians.
bA 100-mm visual analog scale (VAS) was used in which higher scores indicated more active disease.
cA 100-mm VAS was used in which higher scores indicated more severe pain.
dScore range from 0 (best) to 3 (worst).
eThe normal median value is less than 0.287 mg/dL.
DMARDs=disease-modifying antirheumatic drugs; MTX=methotrexate; RF=rheumatoid factor
US-HUMR-190189
