- Inflammatory Bowel Disease Clinic
- SIDE EFFECTS
- Clinical Trials Experience
- Other Adverse Reactions
- Less Common Adverse Reactions In Rheumatoid Arthritis Clinical Studies
- Juvenile Idiopathic Arthritis Clinical Studies
- Psoriatic Arthritis And Ankylosing Spondylitis Clinical Studies
- Adult Crohn’s Disease Clinical Studies
- Pediatric Crohn’s Disease Clinical Studies
- Ulcerative Colitis Clinical Studies
- Plaque Psoriasis Clinical Studies
- Hidradenitis Suppurativa Clinical Studies
- Uveitis Clinical Studies
- Postmarketing Experience
- SIDE EFFECTS
- Adalimumab (Humira)
- Frequently Asked Questions – Adalimumab (Humira)
- Q What is rheumatoid arthritis?
- Q What is tumour necrosis factor alpha (TNFα)?
- Q What is Humira?
- Q How does Humira work?
- Q Is it currently available?
- Q How do I take Humira?
- Q What can I expect from Humira?
- Q What important information do I need to know about side-effects with Humira?
- Q Can I take Humira if I am taking other medicines for my rheumatoid arthritis or other conditions?
- Q How do I store Humira?
- Q: How do I get more information?
- Humira Side Effects
- In Summary
- For the Consumer
- For Healthcare Professionals
- Further information
- More about Humira (adalimumab)
Inflammatory Bowel Disease Clinic
Like all drugs, adalimumab can have side effects, although not everybody will get them. Some side effects can happen almost immediately, others may develop later. It can take up to six months after the last dose for adalimumab to completely leave the body, so some effects might appear even after stopping treatment.
Some adalimumab side effects are likely to be quite mild and may go away on their own. Others can be more serious and will require treatment, or may mean that adalimumab is not suitable for you.
- Reactions to the injection such as pain or swelling, redness, bruising and itching. This can be very common, affecting at least one in 10 people. Using the adalimumab when it is at room temperature or cooling your skin with an ice pack may help. Your doctor or IBD nurse should also be able to advise you on how to reduce this sort of reaction
- Symptoms that mean you are having an allergic reaction to adalimumab. For example, rashes, hives (a raised itchy rash that appears on the skin), a swollen face, hands and feet, or trouble breathing and shortness of breath
- Some of the more common side effects of adalimumab include abdominal pain, nausea, headaches, fatigue and joint pain
WHAT ARE THE MOST LIKELY SIDE EFFECTS?
- A greater chance of suffering from infections such as colds and flu and also some more serious infections such as pneumonia and sepsis (general inflammation and problems with blood clotting). You may also be at greater risk of developing tuberculosis (TB), or of having underlying TB reactivated while on adalimumab. Symptoms of an infection often include feeling very tired, fever, cough, and warm painful skin. You may need to stop the adalimumab if you have an infection, so check with your medical team first if you think you have or are developing an infection
- Blood problems. Your body may not make enough of the blood cells that help fight infections or help to stop bleeding. Symptoms include a fever that does not go away, bruising or bleeding very easily, sore throat, or looking very pale
- Liver problems, you should contact your doctor if your skin or eyes look yellow, you feel very tired with a lack of appetite, or you have a persistent pain on the right hand side of your stomach. Adalimumab can also activate viral hepatitis if you carry it in your blood. Your doctor should check whether you are a carrier before you start treatment, and continue with blood tests while you are on the drug to make sure it does not activate
- Skin reactions such as psoriasis (scaly patches) and eczema, other skin rashes and ulcers. Some of these can be treated without stopping your adalimumab
- Some types of skin cancer. You must tell your doctor if you have a bump or open sore which is not healing. There have also been reports of other cancers including lymphoma (cancer of the lymph glands) as an uncommon side effect of adalimumab, and more rarely still, leukaemia. You may be more at risk if you are also taking immunosuppressive drugs such as azathioprine or methotrexate. However, it is difficult to know what the exact risk is, as cancers in these circumstances happen rarely and very few people are affected
- New heart failure or worsening of heart failure you already have. Call your doctor right away if you get new or worsening symptoms of heart failure while taking adalimumab, including shortness of breath, swelling of your ankles or feet, or sudden weight gain
- Other very rare complications that have been linked to taking adalimumab include demyelination (damage to nerves) and some rare inflammatory conditions, such as lupus (an autoimmune condition). Many of these serious side effects are reversible if the drug is stopped
TELL YOUR DOCTOR IMMEDIATELY IF YOU DEVELOP ANY OF THE FOLLOWING SYMPTOMS
- A severe rash, hives (swollen red patches of skin) or other signs of allergic reaction
- Swollen face, hands and feet
- Trouble breathing or swallowing
- Shortness of breath
- Persistent fever, bruising, bleeding or paleness
- Fatigue, cough, or flu-like symptoms
Overall, it is best to let your doctor or IBD nurse know about any new symptoms you develop while on adalimumab, whenever they occur. Your IBD team should also be able to help with any queries and concerns.
The most serious adverse reactions described elsewhere in the labeling include the following:
- Serious Infections
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The most common adverse reaction with HUMIRA was injection site reactions. In placebocontrolled trials, 20% of patients treated with HUMIRA developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.
The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in patients with RA (i.e., Studies RA-I, RAII, RA-III and RA-IV) was 7% for patients taking HUMIRA and 4% for placebo-treated patients. The most common adverse reactions leading to discontinuation of HUMIRA in these RA studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).
In the controlled portions of the 39 global HUMIRA clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 HUMIRA-treated patients versus a rate of 2.9 per 100 patient-years in 4848 control-treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and postsurgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis .
Tuberculosis And Opportunistic Infections
In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS and UV that included 24,605 HUMIRA-treated patients, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years. In a subgroup of 10,113 U.S. and Canadian HUMIRA-treated patients, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal .
In the rheumatoid arthritis controlled trials, 12% of patients treated with HUMIRA and 7% of placebo-treated patients that had negative baseline ANA titers developed positive titers at week 24. Two patients out of 3046 treated with HUMIRA developed clinical signs suggestive of newonset lupus-like syndrome. The patients improved following discontinuation of therapy. No patients developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with HUMIRA on the development of autoimmune diseases is unknown.
Liver Enzyme Elevations
There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of HUMIRA (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of HUMIRA-treated patients and 1.5% of controltreated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between HUMIRA and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of HUMIRA in patients with polyarticular JIA who were 4 to 17 years, ALT elevations ≥ 3 x ULN occurred in 4.4% of HUMIRA-treated patients and 1.5% of control-treated patients (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of HUMIRA and MTX than those treated with HUMIRA alone. In general, these elevations did not lead to discontinuation of HUMIRA treatment. No ALT elevations ≥ 3 x ULN occurred in the open-label study of HUMIRA in patients with polyarticular JIA who were 2 to <4 years.
In controlled Phase 3 trials of HUMIRA (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult patients with CD with a control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of HUMIRA-treated patients and 0.9% of control-treated patients. In the Phase 3 trial of HUMIRA in pediatric patients with Crohn’s disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these patients discontinued due to abnormalities in ALT tests. In controlled Phase 3 trials of HUMIRA (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ≥3 x ULN occurred in 1.5% of HUMIRA-treated patients and 1.0% of control-treated patients. In controlled Phase 3 trials of HUMIRA (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of HUMIRA-treated patients and 1.8% of control-treated patients. In controlled trials of HUMIRA (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of HUMIRA-treated subjects and 0.6% of control-treated subjects. In controlled trials of HUMIRA (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in adult patients with uveitis with an exposure of 165.4 PYs and 119.8 PYs in HUMIRA-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN occurred in 2.4% of HUMIRA-treated patients and 2.4% of control-treated patients.
Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab during the 6- to 12-month period. Approximately 5% (58 of 1062) of adult RA patients receiving HUMIRA developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate (MTX) had a lower rate of antibody development than patients on HUMIRA monotherapy (1% versus 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of HUMIRA is unknown.
In patients with polyarticular JIA who were 4 to 17 years of age, adalimumab antibodies were identified in 16% of HUMIRA-treated patients. In patients receiving concomitant MTX, the incidence was 6% compared to 26% with HUMIRA monotherapy. In patients with polyarticular JIA who were 2 to <4 years of age or 4 years of age and older weighing <15 kg, adalimumab antibodies were identified in 7% (1 of 15) of HUMIRA-treated patients, and the one patient was receiving concomitant MTX.
In patients with AS, the rate of development of antibodies to adalimumab in HUMIRA-treated patients was comparable to patients with RA.
In patients with PsA, the rate of antibody development in patients receiving HUMIRA monotherapy was comparable to patients with RA; however, in patients receiving concomitant MTX the rate was 7% compared to 1% in RA.
In adult patients with CD, the rate of antibody development was 3%.
In pediatric patients with Crohn’s disease, the rate of antibody development in patients receiving HUMIRA was 3%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 mcg/mL. Among the patients whose serum adalimumab levels were < 2 mcg/mL (approximately 32% of total patients studied), the immunogenicity rate was 10%.
In patients with moderately to severely active UC, the rate of antibody development in patients receiving HUMIRA was 5%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 mcg/mL. Among the patients whose serum adalimumab levels were < 2 mcg/mL (approximately 25% of total patients studied), the immunogenicity rate was 20.7%.
In patients with Ps, the rate of antibody development with HUMIRA monotherapy was 8%. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 mcg/mL. Among the patients whose serum adalimumab levels were < 2 mcg/mL (approximately 40% of total patients studied), the immunogenicity rate was 20.7%. In Ps patients who were on HUMIRA monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal.
Anti-adalimumab antibodies were measured in clinical trials of subjects with moderate to severe HS with two assays (an original assay capable of detecting antibodies when serum adalimumab concentrations declined to < 2 mcg/mL and a new assay that is capable of detecting antiadalimumab antibody titers in all subjects, independent of adalimumab concentration). Using the original assay, the rate of anti-adalimumab antibody development in subjects treated with HUMIRA was 6.5%. Among subjects who stopped HUMIRA treatment for up to 24 weeks and in whom adalimumab serum levels subsequently declined to < 2 mcg/mL (approximately 22% of total subjects studied), the immunogenicity rate was 28%. Using the new titer-based assay, antiadalimumab antibody titers were measurable in 61% of HS subjects treated with HUMIRA. Antibodies to adalimumab were associated with reduced serum adalimumab concentrations. In general, the extent of reduction in serum adalimumab concentrations is greater with increasing titers of antibodies to adalimumab. No apparent association between antibody development and safety was observed.
In adult patients with non-infectious uveitis, anti-adalimumab antibodies were identified in 4.8% (12/249) of patients treated with adalimumab. However, due to the limitation of the assay conditions, antibodies to adalimumab could be detected only when serum adalimumab levels were < 2 mcg/mL. Among the patients whose serum adalimumab levels were < 2 mcg/Ml (approximately 23% of total patients studied), the immunogenicity rate was 21.1%. Using an assay which could measure an anti-adalimumab antibody titer in all patients, titers were measured in 39.8% (99/249) of non-infectious uveitis adult patients treated with adalimumab. No correlation of antibody development to safety or efficacy outcomes was observed.
The data reflect the percentage of patients whose test results were considered positive for antibodies to adalimumab or titers, and are highly dependent on the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to adalimumab with the incidence of antibodies to other products may be misleading.
Other Adverse Reactions
Rheumatoid Arthritis Clinical Studies
The data described below reflect exposure to HUMIRA in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). HUMIRA was studied primarily in placebo- controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg HUMIRA every other week.
Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with HUMIRA 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion.
Table 1: Adverse Reactions Reported by ≥5% of Patients Treated with HUMIRA During Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)
|HUMIRA 40 mg subcutaneous Every Other Week
|Adverse Reaction (Preferred Term)|
|Upper respiratory infection||17%||13%|
|Laboratory test abnormal||8%||7%|
|Alkaline phosphatase increased||5%||3%|
|Injection site reaction **||8%||1%|
|Urinary tract infection||8%||5%|
|* Laboratory test abnormalities were reported as adverse reactions in European trials
** Does not include injection site erythema, itching, hemorrhage, pain or swelling
Less Common Adverse Reactions In Rheumatoid Arthritis Clinical Studies
Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in HUMIRA-treated patients in RA studies were:
Body As A Whole: Pain in extremity, pelvic pain, surgery, thorax pain
Cardiovascular System: Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia
Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, hepatic necrosis, vomiting
Endocrine System: Parathyroid disorder
Hemic And Lymphatic System: Agranulocytosis, polycythemia
Metabolic And Nutritional Disorders: Dehydration, healing abnormal, ketosis, paraproteinemia, peripheral edema
Musculo-Skeletal System: Arthritis, bone disorder, bone fracture (not spontaneous), bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, tendon disorder
Nervous System: Confusion, paresthesia, subdural hematoma, tremor
Respiratory System: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion
Special Senses: Cataract
Thrombosis: Thrombosis leg
Urogenital System: Cystitis, kidney calculus, menstrual disorder
Juvenile Idiopathic Arthritis Clinical Studies
In general, the adverse reactions in the HUMIRA-treated patients in the polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II) were similar in frequency and type to those seen in adult patients . Important findings and differences from adults are discussed in the following paragraphs.
In Study JIA-I, HUMIRA was studied in 171 patients who were 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster.
In Study JIA-I, 45% of patients experienced an infection while receiving HUMIRA with or without concomitant MTX in the first 16 weeks of treatment. The types of infections reported in HUMIRA-treated patients were generally similar to those commonly seen in polyarticular JIA patients who are not treated with TNF blockers. Upon initiation of treatment, the most common adverse reactions occurring in this patient population treated with HUMIRA were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in patients receiving HUMIRA was granuloma annulare which did not lead to discontinuation of HUMIRA treatment.
In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity reactions were seen in approximately 6% of patients and included primarily localized allergic hypersensitivity reactions and allergic rash.
In Study JIA-I, 10% of patients treated with HUMIRA who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment. No patient developed clinical signs of autoimmunity during the clinical trial.
Approximately 15% of patients treated with HUMIRA developed mild-to-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I. Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK levels decreased or returned to normal in all patients. Most patients were able to continue HUMIRA without interruption.
In Study JIA-II, HUMIRA was studied in 32 patients who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with polyarticular JIA. The safety profile for this patient population was similar to the safety profile seen in patients 4 to 17 years of age with polyarticular JIA.
In Study JIA-II, 78% of patients experienced an infection while receiving HUMIRA. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of patients receiving HUMIRA in the study and included dental caries, rotavirus gastroenteritis, and varicella.
In Study JIA-II, non-serious allergic reactions were observed in 6% of patients and included intermittent urticaria and rash, which were all mild in severity.
Psoriatic Arthritis And Ankylosing Spondylitis Clinical Studies
HUMIRA has been studied in 395 patients with psoriatic arthritis (PsA) in two placebocontrolled trials and in an open label study and in 393 patients with ankylosing spondylitis (AS) in two placebo-controlled studies. The safety profile for patients with PsA and AS treated with HUMIRA 40 mg every other week was similar to the safety profile seen in patients with RA, HUMIRA Studies RA-I through IV.
Adult Crohn’s Disease Clinical Studies
HUMIRA has been studied in 1478 adult patients with Crohn’s disease (CD) in four placebocontrolled and two open-label extension studies. The safety profile for adult patients with CD treated with HUMIRA was similar to the safety profile seen in patients with RA.
Pediatric Crohn’s Disease Clinical Studies
HUMIRA has been studied in 192 pediatric patients with Crohn’s disease in one double-blind study (Study PCD-I) and one open-label extension study. The safety profile for pediatric patients with Crohn’s disease treated with HUMIRA was similar to the safety profile seen in adult patients with Crohn’s disease.
During the 4-week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with HUMIRA were injection site pain and injection site reaction (6% and 5%, respectively).
A total of 67% of children experienced an infection while receiving HUMIRA in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis.
A total of 5% of children experienced a serious infection while receiving HUMIRA in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis.
In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions.
Ulcerative Colitis Clinical Studies
HUMIRA has been studied in 1010 patients with ulcerative colitis (UC) in two placebocontrolled studies and one open-label extension study. The safety profile for patients with UC treated with HUMIRA was similar to the safety profile seen in patients with RA.
Plaque Psoriasis Clinical Studies
HUMIRA has been studied in 1696 subjects with plaque psoriasis (Ps) in placebo-controlled and open-label extension studies. The safety profile for subjects with Ps treated with HUMIRA was similar to the safety profile seen in subjects with RA with the following exceptions. In the placebo-controlled portions of the clinical trials in Ps subjects, HUMIRA-treated subjects had a higher incidence of arthralgia when compared to controls (3% vs. 1%).
Hidradenitis Suppurativa Clinical Studies
HUMIRA has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebocontrolled studies and one open-label extension study. The safety profile for subjects with HS treated with HUMIRA weekly was consistent with the known safety profile of HUMIRA.
Flare of HS, defined as ≥25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from HUMIRA treatment following the primary efficacy timepoint in two studies.
Uveitis Clinical Studies
HUMIRA has been studied in 464 adult patients with uveitis (UV) in placebo-controlled and open-label extension studies and in 90 pediatric patients with uveitis (Study PUV-I). The safety profile for patients with UV treated with HUMIRA was similar to the safety profile seen in patients with RA.
The following adverse reactions have been identified during post-approval use of HUMIRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to HUMIRA exposure.
Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis
General disorders and administration site conditions: Pyrexia
Hepato-biliary disorders: Liver failure, hepatitis
Immune system disorders: Sarcoidosis
Neoplasms benign, malignant and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)
Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barre syndrome), cerebrovascular accident
Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism
Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia, lichenoid skin reaction
Vascular disorders: Systemic vasculitis, deep vein thrombosis
Read the entire FDA prescribing information for Humira (Adalimumab Injection Solution for Subcutaneous Administration)
Almost one-third of new drugs approved by U.S. regulators over a decade ended up years later with warnings about unexpected, sometimes life-threatening side effects or complications, a new analysis found.
The results covered all 222 prescription drugs approved by the U.S. Food and Drug Administration from 2001 through 2010. The researchers looked at potential problems that cropped up during routine monitoring that’s done once a medicine is on the market.
The 71 flagged drugs included top-sellers for treating depression, arthritis, infections and blood clots. Safety issues included risks for serious skin reactions, liver damage, cancer and even death.
“The large percentage of problems was a surprise,” and they included side effects not seen during the review process, said Dr. Joseph Ross, the study’s lead author and an associate professor of medicine and public health at Yale University.
While most safety concerns were not serious enough to prompt recalls, the findings raise questions about how thoroughly drugs are tested before approval, said drug safety expert Thomas Moore. But Ross said the results suggest that the FDA “is kind of doing a great job” at scrutinizing drugs after approval.
Related: Speed Up Drug Approvals? FDA Already Did
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New drugs are generally tested first in hundreds or even thousands of people for safety and effectiveness.
“We know that safety concerns, new ones, are going to be identified once a drug is used in a wider population. That’s just how it is,” Ross said. “The fact that that’s such a high number means the FDA is working hard to evaluate drugs and once concerns are identified, they’re communicating them.”
The researchers analyzed online FDA data on new drugs and the agency’s later safety announcements. Problems surfaced on average about four years after approval. Results were published Tuesday in the Journal of the American Medical Association.
The FDA said in a statement that it performs post-market monitoring “to identify new safety information that may impact product labeling.” The agency said it would review the study findings but declined to comment further.
“We know that safety concerns, new ones, are going to be identified once a drug is used in a wider population.”
The study counted black-box warnings for dozens of drugs; these involved serious problems including deaths or life-threatening conditions linked with the drugs. There were also dozens of alerts for less serious potential harms and three drug withdrawals because of the potential for death or other serious harm.
AbilifyDaniel Acker / Bloomberg via Getty Images
Among the drugs with added warnings: Humira, used for arthritis and some other illnesses; Abilify, used for depression and other mental illness; and Pradaxa, a blood thinner. The withdrawn drugs and the reason: Bextra, an anti-inflammatory medicine, heart problems; Raptiva, a psoriasis drug, rare nervous system illness; and Zelnorm, a bowel illness drug, heart problems.
Related: NSAIDs Raise Heart Attack Risk Within a Week
Safety issues were most common for psychiatric drugs and biologic drugs – made from living cells rather than chemicals – than for older drug types. Drugs brought to market through “accelerated” approval were slightly more likely to have later safety issues than those approved through conventional channels, a link seen in some previous research.
In recent years, there has been increasing pressure on the FDA from consumers and others to speed up its regulatory review process to get new drugs to the market sooner, Ross said.
Related: Critics Attack Trump’s Pick to Head FDA
Moore, a senior scientist for drug safety and policy at the Institute for Safe Medication Practices, said the new results raise concerns about whether new drugs are being extensively tested before approval. He noted that since 2011, drugs have increasingly been approved based on studies in small numbers of patients amid public criticism questioning whether the FDA is keeping potential cures away from patients.
“The answer is, you can’t know whether they’re valuable and lifesaving treatments unless you test them” adequately, Moore said.
PhRMA, a drug industry trade group, is reviewing the study, said spokeswoman Holly Campbell. In a statement, she said the industry is committed to post-market surveillance of new medicines, but added, “Even with rigorous clinical studies and regulatory review it may be impossible to detect certain safety signals until several years after approval, once the medicine is in broader use.”
Patients receiving disease-modifying anti-rheumatic drugs (DMARDs) saw no positive dynamics of mental disorders (MD), according to research presented at the 2017 Annual European Congress of Rheumatology (EULAR), held June 14-17 in Madrid, Spain. In addition, patients receiving biologics saw mild positive dynamics of anxiety disorder.
Researchers from the Nasonova Research Institute of Rheumatology in Moscow, Russia, conducted a prospective 5-year study to determine the frequency of MD dynamics when using antidepressants, biologics, and DMARDs.
These results led the researchers to conclude that the best positive dynamics of MD frequency occurred in the RA groups receiving antidepressant treatment in combination with DMARDs and biologics.
Abramkin A, Lisitsyna T, Veltishchev D, Seravina O, Kovalevskaya O, Nasonov E. The dynamics of mental disorders frequency in complex DMARDs, biologics, and antidepressants treatment of rheumatoid arthritis patients. Presented at: 2017 Annual European Congress of Rheumatology (EULAR); June 14-17, 2017; Madrid, Spain. doi:10.1136/annrheumdis-2017-eular.3759
If you are to have surgery and are taking adalimumab, it is important to discuss what to do with your rheumatologist. Depending on the type of surgery, you may be asked to stop your treatment for a short time and wait for wound healing before re-starting adalimumab.
Frequently Asked Questions – Adalimumab (Humira)
These information notes have been prepared for the National Rheumatoid Arthritis Society following your direct request. They represent frequently asked questions about Humira, which is licensed as a treatment option for rheumatoid arthritis in adult patients.
Further information is available on request from: Medical Information, AbbVie Ltd., Abbott House, Vanwall Road, Vanwall Business Park, Maidenhead, Berkshire. Tel: 01628 774920 / [email protected]
Q What is rheumatoid arthritis?
A: Rheumatoid arthritis is a disease of the immune system in which your body’s own defence system attacks the tissues of your joints. Other tissues apart from the joints, such as the lungs, the skin and the eyes, may also be affected.
Q What is tumour necrosis factor alpha (TNFα)?
A: TNFα is a protein in your immune system that is believed to be one of the main causes of joint inflammation in rheumatoid arthritis. Normally, it plays an important role in helping your body fight infections. People with rheumatoid arthritis have too much TNFα in their bodies. This extra TNFα inflames the normal body tissues, including the joints.
Q What is Humira?
A: Humira is a medicine that is usedas a treatment option for people with moderate to severe rheumatoid arthritis. People with rheumatoid arthritis are usually given other medicines for their disease before they are given Humira. Humira is for people with rheumatoid arthritis who have not responded well enough to these other medicines.
Q How does Humira work?
A: Humira is a medicine called a TNF inhibitor, which is a type of protein that blocks the action of a substance your body makes called TNFα. TNFα is made by your body’s immune system. People with rheumatoid arthritis have too much of it in their bodies. The extra TNFα in your body can attack normal healthy body tissues and cause inflammation especially in the tissues in your bones, cartilage, and joints. Humira has been shown to slow down the damage to the cartilage and bone of the joints caused by the disease, and improve physical function.
Q Is it currently available?
A: Humira is available as a treatment option for RA in the United Kingdom.
Q How do I take Humira?
A: Patients give themselves an injection of HUMIRA under the skin once every other week, or more frequently (every week) if your doctor tells them to. The medicine is premixed and premeasured, and comes in a ready-to-use syringe or pen for use in adult patients.
Q What can I expect from Humira?
A: Clinical trials on Humira have indicated that many people using Humira experience relief from the signs and symptoms of rheumatoid arthritis as early as 1-2 weeks. Importantly, TNFα blockers may also help prevent damage to your bones and joints. This is important because, once bone and joint damage from rheumatoid arthritis happens, it is permanent. Joint damage also plays a big part in how you will feel in the future. As with all medicines, Humira will work better for some people than in some people than in others.
Q What important information do I need to know about side-effects with Humira?
A: Any medicine can have side-effects and you must consult your doctor or nurse if you are worried about any symptoms. Like all medicines that affect your immune system, Humira can cause side effects. Many patients experience a reaction where the injection was given. These reactions are usually mild and include redness, rash, swelling, itching or bruising. Usually the rash will go away within a few days. Any pain, redness or swelling around an injection site that doesn’t go away within a few days should be brought to the attention of your doctor or nurse. Other side-effects include upper respiratory infections (sinus infections), headache and nausea. There are various more severe infections that may occur, such as tuberculosis (TB) and malignancies (e.g. lymphoma), however your doctor will discuss these with you. Further information on side-effects is available in the Patient Information Leaflet (PIL) on the Electronic Medicines Compendium (EMC website).
Q Can I take Humira if I am taking other medicines for my rheumatoid arthritis or other conditions?
A: Yes, you can take other medicines prescribed by your doctor while on Humira (e.g. steroids, non-steroidal anti-inflammatory drugs such as aspirin or prescription pain relievers, methotrexate or other disease-modifying anti-rheumatic drugs). It is important that you tell your doctor about any other medicines you are taking for other conditions (for example, high blood pressure medicine) before you start taking Humira. You should also tell your doctor about any over-the-counter drugs, herbal medicines and vitamin and mineral supplements you are taking.
Q How do I store Humira?
A: Humira should be stored at 2 C-8 C (in a refrigerator) in the original container until it is used. It should be protected from light and should not be frozen.
When needed (for example when you are travelling), a single Humira pre-filled pen may be stored at room temperature (up to 25°C) for a maximum period of 14 days – be sure to protect it from light. Once removed from the refrigerator for room temperature storage, the pen must be used within 14 days or discarded, even if it is returned to the refrigerator.
You should record the date when the pen is first removed from refrigerator, and the date after which it should be discarded.
Do not throw away any medicines via wastewater or household waste. Ask your doctor or pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. Any unused product or waste material should be disposed of in accordance with local requirements.
Q: How do I get more information?
A: Please refer to your Humira Patient Information Leaflet for further information. You should discuss any further questions you may have with your doctor or nurse.
References available on request
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Humira Side Effects
Generic Name: adalimumab
Medically reviewed by Drugs.com. Last updated on Dec 15, 2018.
- Side Effects
Note: This document contains side effect information about adalimumab. Some of the dosage forms listed on this page may not apply to the brand name Humira.
Common side effects of Humira include: upper respiratory tract infection, headache, injection site reaction, skin rash, antibody development, sinusitis, and pain at injection site. Other side effects include: urinary tract infection, abdominal pain, and flu-like symptoms. See below for a comprehensive list of adverse effects.
For the Consumer
Applies to adalimumab: subcutaneous solution
Subcutaneous route (Solution)
Patients treated with adalimumab are at increased risk of infection, some of which may become serious and lead to hospitalization or death. These infections have included TB, invasive fungal infections, bacterial, viral, and those caused by opportunistic pathogens including Legionella and Listeria. The risks and benefits of therapy should be carefully considered prior to treatment initiation in patients with chronic or recurrent infection. Evaluate for latent TB and treat if necessary prior to initiating therapy. Monitor patients closely for signs and symptoms of infection during and after treatment, including the possible development of TB in patients who tested negative prior to treatment. Consider empirical antifungal therapy in at-risk patients who develop severe systemic illness. Lymphoma and other malignancies, some fatal, have been reported in pediatric and adolescent patients treated with tumor necrosis factor (TNF) blockers such as adalimumab. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), usually fatal, have been reported in patients treated with TNF blockers including adalimumab, primarily in adolescent and young adult males with Crohn disease and ulcerative colitis. Most cases occurred in patients receiving concomitant treatment with azathioprine or 6-mercaptopurine.
Subcutaneous route (Solution)
Patients treated with adalimumab-atto are at increased risk of infection, some of which may become serious and lead to hospitalization or death. These infections have included TB, invasive fungal infections, bacterial, viral, and those caused by opportunistic pathogens including Legionella and Listeria. The risks and benefits of therapy should be carefully considered prior to treatment initiation in patients with chronic or recurrent infection. Evaluate for latent TB and treat if necessary prior to initiating therapy. Monitor patients closely for signs and symptoms of infection during and after treatment, including the possible development of TB in patients who tested negative prior to treatment. Consider empirical antifungal therapy in at-risk patients who develop severe systemic illness. Lymphoma and other malignancies, some fatal, have been reported in pediatric and adolescent patients treated with tumor necrosis factor (TNF) blockers, including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), usually fatal, have been reported in patients treated with TNF blockers including adalimumab products, primarily in adolescent and young adult males with Crohn disease and ulcerative colitis. Most cases occurred in patients receiving concomitant treatment with azathioprine or 6-mercaptopurine.
Subcutaneous route (Solution)
Patients treated with adalimumab-adbm are at increased risk of infection, some of which may become serious and lead to hospitalization or death. These infections have included TB, invasive fungal infections, bacterial, viral, and those caused by opportunistic pathogens including Legionella and Listeria. The risks and benefits of therapy should be carefully considered prior to treatment initiation in patients with chronic or recurrent infection. Evaluate for latent TB and treat if necessary prior to initiating therapy. Monitor patients closely for signs and symptoms of infection during and after treatment, including the possible development of TB in patients who tested negative prior to treatment. Consider empirical antifungal therapy in at-risk patients who develop severe systemic illness. Lymphoma and other malignancies, some fatal, have been reported in pediatric and adolescent patients treated with tumor necrosis factor (TNF) blockers such as adalimumab-adbm. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), usually fatal, have been reported in patients treated with TNF blockers including adalimumab-adbm, primarily in adolescent and young adult males with Crohn disease and ulcerative colitis. Most cases occurred in patients receiving concomitant treatment with azathioprine or 6-mercaptopurine.
Along with its needed effects, adalimumab (the active ingredient contained in Humira) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking adalimumab:
- Body aches or pain
- ear congestion
- gas with abdominal or stomach pain
- loss of voice
- lower back or side pain
- muscle aches and pains
- nasal congestion
- pain or tenderness around the eyes or cheekbones
- rapid and sometimes shallow breathing
- stomach fullness
- sunken eyes
- trouble sleeping
- warmth on the skin
- wrinkled skin
- Abnormal vaginal bleeding or discharge
- arm, back, or jaw pain
- black, tarry stools
- bleeding from the gums or nose
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blood in the stool or change in bowel habits
- bloody or cloudy urine
- blurred vision
- broken bones
- change in size, shape, or color of an existing mole
- change in skin color
- chest pain, tightness, or heaviness
- clear or bloody discharge from the nipple
- cold hands and feet
- coughing or spitting up blood
- decreased urination
- decreased vision
- difficulty with breathing
- difficulty, burning, or painful urination
- dimpling of the breast skin
- eye pain
- fast, slow, or irregular heartbeat
- frequent urge to urinate
- general feeling of illness
- hair loss
- hives, itching, skin rash
- increased thirst
- inverted nipple
- irregular breathing
- irregular pulse
- light colored stools
- loss of appetite
- lump in the breast or under your arm
- lump or swelling in the abdomen or stomach
- mole that leaks fluid or bleeds
- muscle cramps or spasms
- new mole
- night sweats
- no blood pressure or pulse
- noisy breathing
- numbness or tingling in your arms, legs, or face
- pain, redness, or swelling in the arms or legs without any injury present
- pale skin
- persistent non-healing sore on your skin
- pink growth
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- raised, firm, or bright red patch
- redness or swelling of the breast
- seeing or hearing things that are not there
- sharp back pain just below your ribs
- shiny bump on your skin
- slurred speech or problems with swallowing
- sore on the skin of the breast that does not heal
- sore throat
- sores, ulcers, or white spots on the lips or mouth
- spitting up blood
- stiff neck
- stomach pain
- stopping of the heart
- sudden high fever or low grade fever for months
- swelling of the face, fingers, feet, or lower legs
- swollen glands
- swollen neck veins
- troubled breathing with activity
- trouble thinking
- unexplained bruising or bleeding
- unpleasant breath odor
- unusual tiredness or weakness
- unusual weight gain or loss
- visual disturbances
- vomiting of blood or material that looks like coffee grounds
- yellow skin or eyes
Incidence not known
- Blistering, peeling, or loosening of the skin
- joint or muscle pain
- pinpoint red spots on the skin
- red skin lesions, often with a purple center
- red, irritated eyes
- red, scaling, or crusted skin
- unusual bleeding or bruising
Some side effects of adalimumab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
- Bladder pain
- bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
- pounding in the ears
- Abnormal healing
- decrease in height
- difficulty with moving
- difficulty with walking
- dry mouth
- loss of hearing
- loss of strength or energy
- menstrual changes
- muscle or joint stiffness, tightness, or rigidity
- muscle pain or weakness
- pain in the back, ribs, arms, or legs
- shakiness in the legs, arms, hands, and feet
- swelling or redness in the joints
For Healthcare Professionals
Applies to adalimumab: subcutaneous kit, subcutaneous solution
Common (1% to 10%): Hypertension
Uncommon (0.1% to 1%): Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia, congestive heart failure, peripheral edema, systemic vasculitis, deep vein thrombosis
Rare (less than 0.1%): Vascular occlusion, aortic stenosis, thrombophlebitis, aortic aneurysm
Very common (10% or more): Rash (12%)
Postmarketing reports: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all subtypes including pustular and palmoplantar), alopecia, erythema multiforme, panniculitis
Uncommon (0.1% to 1%): Parathyroid disorder
Common (1% to 10%): Diarrhea, nausea, abdominal pain, vomiting, stomatitis, mouth ulceration
Uncommon (0.1% to 1%): Cholecystitis, cholelithiasis, gastroenteritis, gastrointestinal hemorrhage, gastritis, dyspepsia, gastrointestinal disorder, gastrointestinal hemorrhage, rectal hemorrhage, abdominal bloating
Rare (less than 0.1%): Esophagitis, intestinal stenosis, colitis, enteritis
Frequency not reported: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis
Common (1% to 10%): Urinary tract infection, hematuria
Uncommon (0.1% to 1%): Cystitis, kidney calculus, menstrual disorder, pyelonephritis
Uncommon (0.1% to 1%): Liver failure, hepatitis
Rare (less than 0.1%): Hepatic enzymes increased, hepatic necrosis
Postmarketing reports: Hepatic failure
Frequency not reported: Anaphylaxis, angioneurotic edema
Common (1% to 10%): Flu syndrome
Uncommon (0.1% to 1%): Sarcoidosis
Frequency not reported: Development of autoantibodies
Very common (10% or more): Injection site pain (12%)
Common (1% to 10%): Injection site reaction
Common (1% to 10%): Hypercholesterolemia, hyperlipidemia
Uncommon (0.1% to 1%): Dehydration, ketosis, paraproteinemia, increased alkaline phosphatase
Common (1% to 10%): Back pain
Rare (less than 0.1%): Rhabdomyolysis
Very common (10% or more): Headache (12%)
Very rare (less than 0.01%): Hypertrophic pachymeningitis
Uncommon (0.1% to 1%): Optic neuritis, cataract
Uncommon (0.1% to 1%): Adenoma, Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)
Very common (10% or more): Accidental injury (10%)
Uncommon (0.1% to 1%): Pain in extremity, thorax pain
Rare (less than 0.1%): Pyrexia
Frequency not reported: Sepsis, pain in thorax, opportunistic infections, tuberculosis, histoplasmosis, abscess, joint infection, wound infection, superficial fungal infections
Frequency not reported: Renal pain, renal impairment
Very common (10% or more): Upper respiratory infection (17%), sinusitis (11%), pneumonia, pharyngitis, nasopharyngitis
Uncommon (0.1% to 1%): Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion, interstitial lung disease (including pulmonary fibrosis), pulmonary embolism
Frequency not reported: Cough, upper respiratory infection, pharyngeal edema, nasal congestion, pulmonary edema, pleural effusion, pleurisy
Common (1% to 10%): Mood alterations (including depression), anxiety, insomnia
1. “Product Information. Humira (adalimumab).” Abbott Pharmaceutical, Abbott Park, IL.
2. Cerner Multum, Inc. “Australian Product Information.” O 0
3. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.
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