Humira is made by joining together DNA molecules. It is what’s known as a biologic. While most drugs are made from man-made compounds, biologics are generally made from natural sources such as human or animal proteins.
Scientists can analyze a traditional, synthetic drug that’s made through chemical processes in a lab to determine its various components. However, it can be impossible to identify the components of a complex biologic.
“Biologics can be very sensitive to very minor changes in the complex manufacturing process,” Dr. Yong H. Tsai, a board-certified doctor in rheumatology, allergy and clinical immunology wrote in the Daytona Beach News-Journal. “Small differences in the process can significantly affect the nature of the finished biologic drug and the way it works in the body.”
Biologics may have severe side effects, including serious and even fatal infections, tuberculosis reactivation, injection-site reactions and cancers. Typically, patients must have an inadequate response to conventional medications to be considered for biologics.
What Does Humira Do?
Humira is a tumor necrosis factor-α blocker — or TNF blocker. The drug suppresses the immune system by blocking the activity of TNF.
Humira is designed to stop tumor necrosis factor-α, or TNF, from attacking healthy cells.
TNF is a protein produced naturally by the body’s immune system. Some people with certain autoimmune diseases produce too much TNF. The body’s overproduction of TNF can cause inflammation and lead to diseases such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis.
Humira binds to TNF molecules and blocks the molecules from attaching to healthy cells and attacking them. Humira does not stop the body from making too much TNF, but it is designed to reduce the damaging effects of excess TNF.
In addition to Humira, other TNF blockers include Remicade (infliximab), Enbrel (etanercept), Cimzia (certolizumab pegol) and Simponi (golimumab).
Who Can Use Humira?
The U.S. Food and Drug Administration (FDA) first approved Humira on Dec. 31, 2002 to treat rheumatoid arthritis. Between October 2005 and June 2016, the agency added nine more indications to the anti-inflammatory drug’s label.
The Chicago Tribune has dubbed Humira “the Swiss army knife of pharmaceutical drugs” because it is indicated to treat a slew of conditions affecting the skin, joints, spine and gastrointestinal tract. Even though Humira has 10 approved uses in the U.S. and 14 approved uses abroad, the drug’s manufacturer AbbVie continues to look for ways to extend the drug’s reach and add to the list of people who can use Humira.
In the meantime, pharmacies have filled more than 2.4 million Humira prescriptions in a single year. The drug is marketed to people with symptoms including itchy, painful red patches on the scalp; inflamed lesions around the armpits, groin, buttocks and breasts; stiffness of the spine or inflammation of the colon.
When Humira hit the market in 2002, its sole approved use was treatment in adult patients with moderately to severely active rheumatoid arthritis (RA). Humira is designed to reduce signs and symptoms, induce major clinical response, inhibit the progression of structural damage and improve physical function in these patients. The drug can be used alone or in combination with non-biologic disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate.
Humira is also indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. The drug can be used alone or in combination with methotrexate. Humira’s label warns that some children, adolescents and young adults developed cancers — some fatal — after receiving treatment with TNF-blockers, including Humira./p>
In October 2005, the FDA expanded Humira’s approved uses to include treatment in adults with active psoriatic arthritis (PsA). As with RA patients, PsA patients use Humira to reduce signs and symptoms of their disease, inhibit the progression of structural damage and improve physical function. Doctors can prescribe Humira on its own or in combination with non-biologic DMARDs.
Humira’s label was updated in August 2006, after the FDA approved yet another indication: reducing signs and symptoms in adult patients with active ankylosing spondylitis (AS). AS is a type of progressive arthritis that mainly affects the spine.
Adult patients who have moderately to severely active Crohn’s disease (CD) and who have had an inadequate response to conventional therapy were added to the list of candidates for Humira in 2007. Humira is indicated for reducing signs and symptoms and bringing on remission in these patients as well as in patients who have also lost response to or are intolerant to Remicade.
Humira is also indicated for reducing signs and symptoms, and inducing and maintaining 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 (6-MP ) or methotrexate. Most Humira patients who developed a rare type of cancer called hepatosplenic T-cell lymphoma (which often results in death) were male teenagers or young men with inflammatory bowel disease who were also being treated with Imuran (azathioprine) or Purinethol (6‐mercaptopurine, 6‐MP).
The FDA expanded the list of approved Humira uses to include another gastrointestinal disorder, Ulcerative Colitis (UC), in September 2012. Humira is indicated for bringing on and sustaining 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 (6-MP). Scientists have not established whether Humira is effective in patients who have lost response to or were intolerant to other TNF blockers.
In January 2008, AbbVie gained approval to market Humira for the treatment of adult patients with moderate to severe chronic plaque psoriasis (Ps) who are candidates for systemic therapy or phototherapy. Humira is approved for these patients when other systemic therapies are medically less appropriate and only under the condition that they will be closely monitored and have regular follow-up visits with a physician.
The FDA approved Humira for treatment in adults with moderate to severe hidradenitis suppurativa (HS) in 2015. Also known as acne inversa, this painful, chronic inflammatory skin disease causes lesions around the armpit, groin, buttocks and breast. Before Humira, adults with HS had no approved treatment.
Humira became the first and only FDA-approved non-corticosteroid therapy available for adults with non-infectious intermediate, posterior and panuveitis. The FDA approved this use in June 2016.
Who Should Not Use Humira?
Anyone with an allergy to Humira or to any of its ingredients — including sodium phosphate, sodium citrate, citric acid, mannitol and polysorbate 80 — should not use Humira. Also, patients should tell their doctors of any allergies to rubber or latex. The needle cover on the prefilled syringe contains dry natural rubber.
Patients should not start taking Humira if they have any kind of infections, unless a doctor says it’s OK. Every patient should be tested for tuberculosis (TB) before starting Humira. If a patient tests positive for TB, he or she should start treatment for TB prior to starting Humira.
The drug’s manufacturer also warns against using Humira at the same time as other TNF blockers or biologics — specifically Orencia (abatacept), Kineret (anakinra), Remcade (infliximab), Enbrel (etanercept), Cimzia (certolizumab pegol) or Simponi (golimuma) — because of a possible increased risk for serious infections.
Some patients who were treated with rituximab (Rituxan) followed by a TNF blocker, such as Humira, also showed a higher rate of serious infections. Others who were treated with Humira and Imuran (azathioprine) or Purinethol (mercaptopurine, 6-MP) developed hepatosplenic T-cell lymphoma, a rare, often deadly cancer.
Another interaction to consider is Humira and live vaccines. The FDA advises that children get vaccines as recommended by the CDC before starting Humira. While it may be OK for patients on Humira to get certain vaccinations, they should avoid all live vaccines.
Humira should only be used during pregnancy if needed. The medicine can pass through the placenta during the third trimester of pregnancy and may affect immune response in the fetus. Women should not breastfeed while on Humira.
How to Use Humira
Some TNF blockers are administered intravenously at infusion centers or are injected at the dermatologist’s office. Most patients on Humira can inject the drug at home, though some people will need to visit their doctor’s office for injections.
Though some will need to visit their doctor for injections, most patients on Humira can inject the drug at home.
A patient may self-inject Humira or a caregiver may inject the drug using the Humira Pen or prefilled syringe. The Humira Pen is designed so the patient does not see the needle.
Humira must be stored in a refrigerator but may be brought to room temperature for about 15 to 30 minutes before it’s injecting into the abdomen or front thigh. Aside from the needle prick, patients have reported feeling “a sting” from the Humira itself.
It’s important to rotate injection sites to reduce sensitivity and avoid increasingly painful injections. Patients and caregivers should not inject Humira into areas where the skin is tender, bruised, red or hard.
Potential Side Effects of Humira
Users may experience an injection-site reaction — one of the most common side effects of Humria. The FDA received reports of more than 10,000 cases of injection site reactions related to Humria in 2014. Injection-site reactions include redness, rash, swelling, itching or bruising. Symptoms typically go away within a few days. However, patients should call a doctor immediately if they have pain, redness or swelling around the injection site that doesn’t go away within a few days or gets worse.
The other most commonly reported side effects include respiratory issues — specifically upper respiratory infection and sinusitis — headache and rash.
During clinical trials involving nearly 1,400 people, 17 percent of patients treated with Humira reported upper respiratory infection compared with 13 percent of people who received a placebo. Another 11 percent of Humira-treated patients reported sinusitis while only 9 percent of people given the placebo reported the condition.
Headache and rash were each reported by 12 percent of Humira-treated patients. Eight percent and 6 percent of placebo-treated patients reported headache and rash, respectively.
|Side Effects||Humira (705 patients)||Placebo (690 patients)|
|Upper Respiratory Infection||17%||13%|
Other reported side effects were flu syndrome, nausea, abdominal pain, abnormal laboratory tests, high amounts of cholesterol in the blood, high levels of fat particles in the blood, blood in urine, increased alkaline phosphatase, accidental injury, back pain, urinary tract infection and hypertension.
Humira suppresses the immune system, so it can put users at a greater risk of serious or even deadly infections and illnesses. These include tuberculosis (TB) and invasive fungal infections, and cancers of the immune system known as lymphomas.
The FDA requires Humira’s label carry a black box warning — the agencies toughest warning — for serious infections leading to hospitalization or death, including TB, bacterial sepsis, invasive fungal infections and infections due to opportunistic pathogens. The boxed warning also includes cancer, notably lymphoma and hepatosplenic T-cell lymphoma.
Humira warnings include:
- Serious infections
- Injection site reactions
- Severe allergic reactions
- Hepatitis B reactivation
- Neurological reactions
- Blood reactions
- Worsening congestive heart failure
- Lupus-like syndrome
Reported Deaths and Adverse Events
Humira was linked to more than 209,000 adverse event reports between 2013 and 2017, including more than 4,200 deaths. In 2014 and 2015, more people submitted adverse event reports directly to the FDA for Humira than for any other drug.
Humira accounted for 1,581 direct reports to the FDA in 2015 alone. Direct reports are submitted straight to the FDA, rather than through drug manufacturers. Overall, the drug was named in 7,300 domestic serious reports, 34,035 non-serious reports and 8,592 foreign reports.
The drug also ranked first in 2014 in the number of total reports reaching the FDA, and it ranked No. 2 for reports of serious injuries occurring in the U.S. The FDA received 46,937 reports of adverse events associated with Humira — 1,125 cases resulted in deaths while 12,270 resulted in serious injuries. More than 39,600 reports came from within the U.S. Consumers reported about 34,500 adverse events while doctors and others reported about 12,300.
Among serious and fatal injuries reported, 3,298 — or roughly 25 percent — were indicated an infection. Serious injuries for Humira included 1,410 cases of cancer. Just shy of 200 cancer cases resulted in deaths. Humira was also blamed for 1,438 cases of hypersensitivity.
In April and May 2017, AbbVie spent just shy of $50 million in Humira advertisements. The drug maker reserved eight spots in May alone: two for arthritis, four for ulcerative colitis and Crohn’s, and two for psoriasis. The biggest-ticket ad was “Volunteering,” a $10.9 million ad for arthritis.
One box of Humira contains two syringes and costs about $4,500.
The $50 million for advertisements is nothing compared to the $17.6 billion Humira is forecast to generate in 2017. Humira is AbbVie’s single largest product and accounted for more than 60 percent of the company’s revenue in 2014, 2015 and 2016.
Humira generated $16 billion in global sales in 2016, $14 billion in 2015 and $12.5 billion in 2014. U.S. profits reached $10.4 million in 2016, a 24 percent increase from $8.4 million in 2015 and an even bigger jump from $6.5 million in 2014.
Abbvie’s former owner, Abbott Laboratories, paid $7 billion to acquire Knoll Pharmaceuticals and get Humira back in 2001.
The U.S. has seen a surge in prescriptions for Humira in recent years, increasing from 1.5 million prescriptions in 2011 to 2.4 million in 2015. Humira was the most widely prescribed TNF blocker in 2015, with 634,000 dispensed outpatient prescriptions in the fourth quarter of that year. The drug accounted for 558,059 dispensed outpatient prescriptions in the fourth quarter of 2014.
A box of Humira contains two syringes. Before discounts and rebates, the box costs about $4,500. AbbVie tends to increase the price of Humira twice each year. In January 2017, the company hiked up the price of Humira by 8.4 percent. In 2016, the company increased the price by 9.9 percent in January and 7.9 percent in June. The cost of the Humira Pen rose by more than 13 percent per year over 10 years, from $1,258 to $4,441.
In 2016, however, the FDA approved a biosimilar — or near-copy of Humira — called Amjevita. Developed by Amgen Inc., Amjevita is approved for nearly all of the conditions listed on Humira’s label.
Emily Miller is an award-winning writer who has held editorial positions with reputable print and online publications around the U.S. As the editor of Drugwatch.com, Emily draws on her background as both a patient and a journalist to ensure her team of writers provides consumers with the latest and most accurate information on drugs, medical devices, procedures and related lawsuits. Emily holds five Health Literacy certificates from the Centers for Disease Control and Prevention as well as a Bachelor of Science in Journalism from the University of Florida. She is a member of The Alliance of Professional Health Advocates, the American Association for the Advancement of Science, the Society of Professional Journalists and the Society for Technical Communication.
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