Serious Infections: Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Malignancies: 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.
Other Serious Adverse Reactions: Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.
Adult Crohn’s Disease: 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. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
Ulcerative Colitis: 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.
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.
In some patients, the disease can be progressive. Therefore, it is important to regularly re-assess patients after UC diagnosis for worsening of disease by monitoring for3, 5-7:
Currently, there are no formal recommendations regarding these risk factors, but some evidence suggests these could be associated with a more complicated disease course.
No single therapeutic approach can be applied to all patients11; therefore, quickly evaluating treatment response is essential.5,6
Proactive monitoring and prompt adjustment of therapy may be needed to effectively manage persistently active disease.
Timely treatment of moderate to severe UC based on clinical evidence3
HUMIRA (adalimumab) clinical trials included adults with active moderate to severe UC* despite previous†/current treatment with immunosuppressants12,13
*Defined as total Mayo score of 6-12 with an endoscopy subscore of 2-3.
†Within previous 5 years of study.
Anti-TNF=anti-tumor necrosis factor.
bEach patient serves as his or her own control to establish normal stool frequency and the degree of abnormal stool frequency.
cThe daily bleeding score represents the most severe bleeding of the day.
dThe PGA acknowledges the 3 other subscores, the subject’s daily record of abdominal discomfort and functional assessment, and other observations such as physical findings, and the subject’s performance status.
Inflammation can lead to symptoms of CD4:
In CD, the majority of patients present with uncomplicated disease16; however 60% of patients will eventually develop complications due to inflammation-driven tissue damage, some of which may be irreversible and more difficult to treat.16,17
It is important to regularly re-assess patients after CD diagnosis for worsening disease by monitoring for:
CD activity levels defined by the American College of Gastroenterology (ACG)15
*Asymptomatic or without inflammatory sequelae following medical or surgical intervention, no residual active disease, not steroid dependent.
†Ambulatory, able to tolerate oral alimentation without manifestations of dehydration, toxicity, abdominal tenderness, painful mass, obstruction, or >10% weight loss.
‡Failed response to treatment for mild to moderate disease or with more prominent symptoms (fever, weight loss, abdominal pain or tenderness, intermittent nausea or vomiting without obstruction), or significant anemia.
§Persistent symptoms despite corticosteroids or biologics; high fevers, persistent vomiting, evidence of intestinal obstruction, rebound tenderness, cachexia, or abscess.
Crohn's Disease Activity Index (CDAI) is a tool used to quantify the signs and symptoms of adult patients with CD. CDAI score is calcuated by adding the following weighted variables19:
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.
For full Prescribing Information, visit rxabbvie.com/pdf/humira.pdf
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066-2078. 3. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults; American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523. 4. Friedman S, Blumberg RS. Inflammatory bowel disease. In: Kasper D, Fauci A, Hauser S, Longo DL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill Education; 2015:1947-1964. 5. Panaccione R, Rutgeerts P, Sandborn WJ, et al. Review article: treatment algorithms to maximize remission and minimize corticosteroid dependence in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2008;28(6):674-688. 6. Torres J, Billioud V, Sachar DB et al. Ulcerative colitis as a progressive disease; the forgotten evidence. Inflamm Bowel Dis. 2012;18(7):1356-1363. 7. Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380(9853):1606-1619. 8. Yarur AJ, Strobel SG, Deshpande AR, et al. Predictors of aggressive inflammatory bowel disease. Gastroenterol Hepatol (NY). 2011;7(10):652-659. 9. Blonski W, Buchner AM, Lichtenstein GR. Clinical predictors of aggressive/disabling disease: ulcerative colitis and Crohn disease. Gastroenterol Clin North Am. 2012;41(2):443-462. 10. Data on File ABVRRTI62322. 11. Stone CD. Sequential and combination therapy for small bowel Crohn’s disease. In: Bayless TM, Hanauer SB, eds. Advanced Therapy in Inflammatory Bowel Disease. 3rd ed. Shelton, CT: People’s Medical Publishing House—USA; 2011:625-630. 12. Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60(6):780-787. 13. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142(2):257-265. 14. Ha C. Clinical measure of disease activity. In: Bayless TM, Hanauer SB, eds. Advanced Therapy in Inflammatory Bowel Disease. 3rd ed. Shelton, CT: People's Medical Publishing House—USA; 2011:125-130. 15. Lichtenstein GR, Hanauer SB, Sandborn WJ; and the Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104(2):465-483. 16. Thia KT, Sandborn WJ, Harmsen WS, et al. Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology. 2010;139(4):1147-1155. 17. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785-1794. 18. Data on File ABVRRTI62323. 19. Sands BE, Siegel CA. Crohn’s disease. In: Feldman M, Friedman LS, Brant LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th ed. Philadelphia, PA: Saunders Elsevier; 2010:1941-1973.