Abbott announces three-year long-term data evaluating efficacy with HUMIRA® (Adalimumab)

Abbott today announced results from an analysis of three-year long-term data from an ongoing open-label extension of the HUMIRA® (adalimumab) ULTRA 1 and ULTRA 2 studies. Adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to certain other medications and were treated with HUMIRA were evaluated for symptom improvement for up to three years. In this long-term analysis, ulcerative colitis activity was assessed using the Partial Mayo score, which does not include endoscopic findings. Results showed:

• A reduction in observed mean Partial Mayo score (a measure of disease activity that ranges from 0 to 9) from 5.9 at the time of first dose of HUMIRA to 1.4 at week 172 of HUMIRA therapy.
• A 55.3 percent remission rate, per Partial Mayo score at week 60 of the extension study (reflecting 112 weeks from lead-in study baseline), as assessed in the intent-to-treat patients who enrolled in the open-label study extension.

The data were presented this week at the American College of Gastroenterology (ACG) Annual Scientific Meeting in Las Vegas, Nevada, and the United European Gastroenterology Week (UEGW) Annual Meeting in Amsterdam, The Netherlands.

“We know ulcerative colitis can be a long-term, disruptive and difficult-to-treat disease,” said lead investigator Jean-Frédéric Colombel, M.D., professor of gastroenterology and hepatogastroenterology, director of the Department of Hepatogastroenterology, Hôpital Huriez, Lille, France. “These results provide valuable information and insight to further study the long-term use of adalimumab in the treatment of ulcerative colitis.”

UC is an inflammatory bowel disease marked by ulcers in the coloni and may lead to life-threatening complications.ii It is estimated that 25 percent of patients with UC may undergo surgical removal of the colon during their lifetimes, leaving patients with a permanent colostomy or ileal pouch.iii

“These results are encouraging, as they follow the recent regulatory approvals in the U.S. and Europe of HUMIRA for inducing and sustaining clinical remission in adult patients with moderately to severely active UC who demonstrated an inadequate response to immunosuppressant therapy,” said John Medich, Ph.D., divisional vice president, clinical development, Immunology, Abbott. “Abbott is committed to further investigate the long-term use, efficacy and safety of HUMIRA in these patients.”

Study Details

The analysis of the ULTRA 1 and ULTRA 2 trials and the ongoing, multicenter open-label extension evaluated the long-term treatment of HUMIRA in patients with moderately to severely active UC for up to three years (172 weeks). Partial Mayo score (PMS), which evaluates stool frequency, rectal bleeding, and physician’s global assessment, was collected at every study visit during the trials and the open-label extension. Mean PMS over time from first dose of HUMIRA was assessed using observed case method and decreased over time through 172 weeks of treatment from 5.9 (n=992) to 1.4 (n=136).

Of the 588 patients in the intent-to-treat population, 55.3 percent achieved clinical remission (defined s Partial Mayo score of two or less, with no individual subscore greater than one) at week 60 of the open-label extension (n=325). These results were observed for up to three years. Of the 588 patients who entered the open-label extension trial, 141 were receiving HUMIRA 40 mg weekly. An additional 100 patients began receiving HUMIRA 40 mg weekly during the open-label phase due to flare or non-response. The recommended dose of HUMIRA for adult patients with UC is 160 mg on Day 1, followed by 80 mg on Day 15, following two weeks later (Day 29) with 40 mg every other week by subcutaneous injection. In the open-label extension, both the investigator and patient knew that they were receiving HUMIRA. Additionally, open-label extension data may be enriched as patients who remain in the study long-term tend to do better than those who drop out. The results from the placebo-controlled, phase 3 trials demonstrated statistically significant percentages of clinical remission per Mayo score at eight and 52 weeks in HUMIRA-treated patients compared to placebo. The safety results were consistent with the known safety profile of HUMIRA and no new safety signals were observed.

About ULTRA 1iv

ULTRA 1 was an eight week, multi-center, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of HUMIRA for the induction of clinical remission per Mayo score in 390 anti-TNF naïve adult patients who had moderately to severely active UC despite concurrent or prior treatment with immunosuppressants (i.e., corticosteroids, azathioprine, or 6-mercaptopurine).

Mayo score is a measure of disease activity that ranges from 0 to 12 and includes stool frequency, rectal bleeding, endoscopic findings and physician’s global assessment. Patients were randomized to treatment with HUMIRA 160/80 mg (160 mg, week zero; 80 mg, week two; 40 mg, weeks four and six), HUMIRA 80/40 mg (80 mg, week zero; 40 mg; weeks two, four and six) or placebo. Patients, including those randomized to placebo, continued conventional therapy such as corticosteroids, aminosalicylates and immunosuppressants. The primary efficacy endpoint was clinical remission

At week eight, 18 percent of 130 patients in the HUMIRA 160/80 group (p=0.031 vs. placebo) and 10 percent of the 130 in the HUMIRA 80/40 group (p=0.833 vs. placebo) compared with 9 percent of the 130 patients in the placebo group were in clinical remission. The safety results were consistent with the known safety profile of HUMIRA and no new safety signals were observed.

About ULTRA 2v

ULTRA 2 was a 52-week, double-blind, randomized, placebo-controlled phase 3 trial of 494 adult patients who had moderately to severely active UC despite concurrent or prior treatment with immunosuppressants (i.e., corticosteroids, azathioprine, or 6-mercaptopurine). Patients were randomized 1:1 to placebo or HUMIRA (160 mg, week zero; 80 mg, week two; 40 mg every other week starting at week four). Patients, including those randomized to placebo, continued concurrent therapy such as corticosteroids, aminosalicylates and immunosuppressants. Co-primary endpoints were the proportion of patients with clinical remission at week eight and clinical remission at week 52. Clinical remission was defined as a Mayo score of two or less with no individual subscore greater than one.

Of the 248 patients treated with HUMIRA in ULTRA 2,17 percent achieved clinical remission compared to 9 percent on placebo at week eight (p<0.05). At week 52, 17 percent achieved clinical remission compared to 9 percent on placebo (p<0.05). These results were statistically significant compared to placebo. The safety results from ULTRA 2 were consistent with the known safety profile of HUMIRA and no new safety signals were identified.

About UC

UC is an inflammatory bowel disease marked by inflammation in the rectum and colon,vi resulting in diarrhea, rectal bleeding and abdominal cramping.vii Typically, people are diagnosed with UC in their mid-30s, though the disease can occur at any age.vii,viii

The symptoms of UC tend to come and go, with varying periods of clinical stability punctuated by episodic flares of disease activity.vi Severe flares of UC can necessitate hospitalization and can be life-threatening. Treatment may include medication and/or surgery.iii

About HUMIRA

HUMIRA is used in adults to help get moderate to severe ulcerative colitis under control (induce remission) and keep it under control (sustain remission) when certain other medicines have not worked well enough. It is not known if HUMIRA is effective in people who stopped responding to or could not tolerate anti-TNF medicines.

Globally, uses and prescribing information vary; please refer to the individual country label for complete information.

Important Safety Information

HUMIRA is a TNF blocker medicine that affects the immune system and can lower the ability to fight infections. Serious infections have happened in people taking HUMIRA. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections. People should be tested for TB before HUMIRA use and monitored for signs and symptoms of TB during therapy. People at risk of TB may be treated with medicine for TB. Treatment with HUMIRA should not be started in a person with an active infection, unless approved by a doctor. HUMIRA should be stopped if a person develops a serious infection. People should tell their doctor if they live in or have been to a region where certain fungal infections are common, have had TB, hepatitis B, are prone to infections, or have symptoms such as fever, fatigue, cough, or sores.

For people taking TNF blockers, including HUMIRA, the chance of getting lymphoma or other cancers may increase. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers including HUMIRA, the chance of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life threatening if treated.

Other possible serious side effects with HUMIRA include hepatitis B infection in carriers of the virus, allergic reactions, nervous system problems, blood problems, certain immune reactions, including a lupus-like syndrome, liver problems, and new or worsening heart failure or psoriasis. The use of HUMIRA with anakinra or abatacept is not recommended. People using HUMIRA should not receive live vaccines.

Common side effects of HUMIRA include injection site reactions (redness, rash, swelling, itching, or bruising), upper respiratory infections (including sinus infections), headaches, rash, and nausea.

HUMIRA is given by injection under the skin.

The benefits and risks of HUMIRA should be carefully considered before starting therapy.

Full Prescribing Information for HUMIRA is available at http://www.rxabbott.com/pdf/humira.pdf.

References

i National Institutes of Health Website. “Colonic Disease.” http://www.nlm.nih.gov/medlineplus/colonicdiseases.html Last accessed October 3, 2012.

ii Huber, W. (2010) “Life-Threatening Complications of Crohn’s Disease and Ulcerative Colitis: A Systematic Analysis of Admissions to an ICU During 18 Years.” Dtsch Med Wochenschr. 2010 Apr;135(14):668-74. Epub 2010 Mar 31.

iii Crohn’s & Colitis Foundation of America. “Surgery for Ulcerative Colitis.”

http://www.ccfa.org/what-are-crohns-and-colitis/what-is-ulcerative-colitis/colitis-treatment-options.html Last accessed October 3, 2012.

iv Reinisch, W, et al. (2011) “Adalimumab For Induction Of Clinical Remission In Moderately To Severely Active Ulcerative Colitis: Results Of A Randomised Controlled Trial.” Gut. 60:780–787.

v Sandborn, W, et al. (2012) “Adalimumab Induces and Maintains Clinical Remission in Patients With

Moderate-to-Severe Ulcerative Colitis.” Gastroenterology. 142:257–265.

vi Mitros F, Rubin E, (2008) “The Gastrointestinal Tract.” Rubin’s Pathology: Clincopathologic Foundation of Medicine. 549-600.

vii Sands, B (2008) “Fulminant Colitis.” Journal of Gastrointestinal Surgery. 12:2157-2159.

viii Friedman, S, Blumberg R, (2008) “Inflammatory Bowel Disease.” Harrison’s Principles of Internal Medicine. 1886-1899.