For adult patients with active ankylosing spondylitis (AS)
US-MULT-230356
ATLAS study design intro: Double-blind trial of adult patients with active AS. 315 patients were randomized to receive HUMIRA 40 mg EOW (n=208) or placebo (n=107). The co-primary endpoints were percentage of ASAS20 responders at Week 12 and change in mSASSS from baseline to Week 104 for HUMIRA vs OASIS cohort.1-3
ASAS=Assessment of SpondyloArthritis international Society; EOW=every other week; mSASSS=modified Stoke AS Spinal Score; OASIS=Outcome in AS International Study (a historical control cohort of TNF antagonist naïve patients)
NRI analysisb
aP<0.001
bAnalysis is of the intent-to-treat population (patients who received at least 1 dose of the study medication), using nonresponder imputation (NRI) methodology. Patients who withdrew, had missing values, or received early-escape open-label therapy were considered nonresponders.2
ASAS=Assessment of SpondyloArthritis international Society; EOW=every other week; mSASSS=modified Stoke AS Spinal Score; OASIS=Outcome in AS International Study (a historical control cohort of TNF-antagonist-naïve patients); OLE=open-label extension
LOCF analysisc
Subjects with a zero score at baseline are not included in the analysis of percent change from baseline.
aP<0.001
bMorning stiffness, also referred to as inflammation, is represented by the mean of question 5 and 6 BASDAI (the severity and duration of morning stiffness), mean SD (0–10-cm VAS).2
cLast observation carried forward (LOCF) analysis of intent-to-treat population. If a patient received early-escape open-label prior to Week 24, the last observation prior to early-escape open-label was carried forward.2
ASAS=Assessment of SpondyloArthritis international Society; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; EOW=every other week
DATA LIMITATIONS
Change from baseline in total back pain at Week 2 was a non-ranked endpoint not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
ASAS=Assessment of SpondyloArthritis international Society; EOW=every other week; VAS=visual analog scale
NRI analysisb
aP<0.001
bAnalysis of the intent-to-treat population (patients who received at least 1 dose of the study medication), using nonresponder imputation (NRI) methodology. Patients who withdrew, had missing values, or received "early‑escape" open-label therapy were considered nonresponders.2
*Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a composite index including questions on severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness, measured on 0-10 VAS scale. BASDAI50 response is defined as at least a 50% improvement over baseline.2
EOW=every other week; VAS=visual analog scale
Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice.
ASAS=Assessment of SpondyloArthritis international Society; PYs=patient-years; RCT=randomized controlled trial
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, or with underlying conditions that may predispose them to infections. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA.
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 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.
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.
*Non-infectious (NI) intermediate, posterior, or panuveitis.
Ankylosing Spondylitis (AS): HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
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:
SELECT BASELINE CHARACTERISTICS | HUMIRA GROUP (n=208) | Placebo Group (n=107) |
Demographics | ||
Mean age (years) | 41.7 | 43.4 |
Male | 75.5% | 73.8% |
White | 97.1% | 92.5% |
Disease duration (years) | ||
AS | 11.3 | 10.0 |
History (% patients) | ||
HLA-B27 (+) | 78.4 | 79.4 |
Peripheral arthritis | 5.8 | 10.3 |
Uveitis | 32.7 | 25.2 |
Psoriasis | 7.7 | 15.9 |
Crohn’s disease | 2.9 | 0.9 |
Ulcerative colitis | 4.3 | 0.9 |
Symptoms in AS—ASAS components (0-10 cm VAS) (mean) | ||
Patient’s global assessment of disease activity | 6.3 | 6.5 |
Total back pain score | 6.4 | 6.7 |
Inflammation (morning stiffness; discomfort + duration)a | 6.7 | 6.7 |
BASFI | 5.2 | 5.6 |
Physician’s global assessment of disease activity (0-10 cm VAS) (mean) | 5.6 | 5.8 |
BASMI score (range 0-10) (mean) | 3.8 | 4.2 |
BASDAI score (0-10 cm VAS) (mean) | 6.3 | 6.3 |
Signs and symptoms (mean) | ||
Chest expansion (cm) | 3.4 | 3.0 |
MASES (range 0-13) | 6.4 | 6.7 |
Patients with scores >0 | 73.1% | 75.7% |
BAS-G (0-10 cm VAS) | 6.8 | 6.9 |
CRP (mg/dL) | 1.8 | 2.2 |
Tender joint count score (range 0-46 joints) | 5.1 | 5.6 |
Swollen joint count score (range 0-44 joints) | 1.5 | 1.4 |
Patients with ≥1 swollen joint | 36.1% | 41.1% |
Quality of life and physical function (MEAN) | ||
ASQoL Questionnaire score (range 0-18) | 10.2 | 10.6 |
SF-36 PCS score | 32.9 | 31.8 |
Concomitant therapies (%) | ||
Concomitant DMARDs | 19.2 | 20.6 |
Sulfasalazine | 12.5 | 14.0 |
MTX | 9.6 | 7.5 |
Leflunomide | 0 | 0.9 |
Concomitant oral corticosteroids | 12.0 | 5.6 |
Concomitant NSAIDs | 79.8 | 78.5 |
aCalculated as mean of Questions 5 and 6 of the BASDAI
AS=ankylosing spondylitis; ASAS=Assessment of SpondyloArthritis international Society; ASQoL=Ankylosing Spondylitis Quality of Life; BAS-G=Bath Ankylosing Spondylitis patient Global Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASFI=Bath Ankylosing Spondylitis Functional Index; BASMI=Bath Ankylosing Spondylitis Metrology index (sum of the scores of the 5 individual items that are scored on a 0–2 scale); CRP=C reactive protein; DMARDs=disease modifying antirheumatic drugs; HLA=human leukocyte antigen; MASES=Maastricht Ankylosing Spondylitis Enthesitis Score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; RF=rheumatoid factor; SF-36 PCS=Short Form 36 Health Survey (Physical Component Score); VAS=visual analog scale
US-HUM-210672
US-HUM-210672
US-HUM-220513