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Humira (Adalimumab) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Clinical Studies Experience

The most serious adverse reactions were [see Warnings and Precautions (5)]:

  • Serious Infections
  • Neurologic Reactions
  • Malignancies

The most common adverse reaction with HUMIRA was injection site reactions. In placebo-controlled 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 necessitatedrug discontinuation.

The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of Studies RA-I, RA-II, 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 were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).

Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not predict the rates observed in a broader patient population in clinical practice.

Infections

In placebo-controlled rheumatoid arthritis trials, the rate of infection was 1 per patient-year in the HUMIRA-treated patients and 0.9 per patient-year in the placebo-treated patients. The infections consisted primarily of upper respiratory tract infections, bronchitis and urinary tract infections. Most patients continued on HUMIRA after the infection resolved. The incidence of serious infections was 0.04 per patient-year in HUMIRA treated patients and 0.02 per patient-year in placebo-treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions ].

Tuberculosis and Opportunistic Infections

In completed and ongoing global clinical studies that include over 13,000 patients, the overall rate of tuberculosis is approximately 0.26 per 100 patient-years. In over 4500 patients in the US and Canada, the rate is approximately 0.07 per 100 patient-years. These studies include reports of miliary, lymphatic, peritoneal, as well as pulmonary. Most of the cases of tuberculosis occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. Cases of opportunistic infections have also been reported in these clinical trials at an overall rate of approximately 0.075/100 patient-years. Some cases of opportunistic infections and tuberculosis have been fatal [see Warnings and Precautions].

Malignancies

More cases of malignancy have been observed in HUMIRA-treated patients compared to control-treated patients in clinical trials [see Warnings and Precautions ].

Autoantibodies

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 new-onset 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.

Immunogenicity

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 rheumatoid arthritis patients receiving HUMIRA developed low-titer antibodies to adalimumab at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate 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 ankylosing spondylitis, the rate of development of antibodies to adalimumab in HUMIRA-treated patients was comparable to patients with rheumatoid arthritis. In patients with psoriatic arthritis, the rate of antibody development in patients receiving HUMIRA monotherapy was comparable to patients with rheumatoid arthritis; however, in patients receiving concomitant methotrexate the rate was 7% compared to 1% in rheumatoid arthritis. In patients with Crohn's disease, the rate of antibody development was 2.6%.

The data reflect the percentage of patients whose test results were considered positive for antibodies to adalimumab in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally the observed incidence of antibody positivity in an assay may be influenced by several factors including 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

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. Adverse reaction rates in patients treated with HUMIRA 40 mg weekly were similar to rates in patients treated with HUMIRA 40 mg every other week. 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 Rheumatoid Arthritis Studies
HUMIRA


40 mg subcutaneous


Every Other Week

Placebo
(N=705)(N=690)
Adverse Reaction (Preferred Term)PercentagePercentage
*  Laboratory test abnormalities were reported as adverse reactions in European trials

** Does not include erythema and/or itching, hemorrhage, pain or swelling

   Respiratory   
     Upper respiratory infection1713
     Sinusitis119
     Flu syndrome76
Gastrointestinal
     Nausea98
     Abdominal pain74
Laboratory Tests*
     Laboratory test abnormal87
     Hypercholesterolemia64
     Hyperlipidemia75
     Hematuria54
     Alkaline phosphatase increased53
Other
     Injection site pain1212
     Headache128
     Rash126
     Accidental injury108
     Injection site reaction **81
     Back pain64
     Urinary tract infection85
     Hypertension53

Other Adverse Reactions

Other infrequent serious adverse reactions occurring at an incidence of less than 5% in rheumatoid arthritis patients treated with HUMIRA were:

Body As A Whole: Fever, infection, pain in extremity, pelvic pain, sepsis, surgery, thorax pain, tuberculosis reactivated

Cardiovascular System: Arrhythmia, atrial fibrillation, cardiovascular disorder, chest pain, congestive heart failure, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia, vascular disorder

Collagen Disorder: Lupus erythematosus syndrome

Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal disorder, gastrointestinal hemorrhage, hepatic necrosis, vomiting

Endocrine System: Parathyroid disorder

Hemic And Lymphatic System: Agranulocytosis, granulocytopenia, leukopenia, lymphoma like reaction, pancytopenia, polycythemia [see Warnings and Precautions]

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

Neoplasia: Adenoma, carcinomas such as breast, gastrointestinal, skin, urogenital, and others; lymphoma and melanoma.

Nervous System: Confusion, multiple sclerosis, paresthesia, subdural hematoma, tremor

Respiratory System: Asthma, bronchospasm, dyspnea, lung disorder, lung function decreased, pleural effusion, pneumonia

Skin And Appendages: Cellulitis, erysipelas, herpes zoster

Special Senses: Cataract

Thrombosis: Thrombosis leg

Urogenital System: Cystitis, kidney calculus, menstrual disorder, pyelonephritis

Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies

HUMIRA has been studied in 395 patients with psoriatic arthritis in two placebo-controlled trials and in an open label study and in 393 patients with ankylosing spondylitis in two placebo-controlled studies. The safety profile for patients with psoriatic arthritis and ankylosing spondylitis treated with HUMIRA 40 mg every other week was similar to the safety profile seen in patients with rheumatoid arthritis, HUMIRA Studies RA-I through IV. In the clinical trials of patients with psoriatic arthritis and ankylosing spondylitis, elevations of aminotransferases were observed (ALT more common than AST) in a greater proportion of patients receiving HUMIRA than in controls, both when HUMIRA was given as monotherapy and when it was used in combination with other immunosuppressive agents. Most elevations of ALT and AST observed were in the range of 1.5 to 3 times the upper limit of normal. In general, patients who developed ALT and AST elevations were asymptomatic, and the abnormalities decreased or resolved with either continuation or discontinuation of HUMIRA, or modification of concomitant medications.

Crohn’s Disease Clinical Studies

HUMIRA has been studied in 1478 patients with Crohn’s disease in four placebo-controlled and two open-label extension studies. The safety profile for patients with Crohn’s disease treated with HUMIRA was similar to the safety profile seen in patients with rheumatoid arthritis.

Postmarketing Experience

Adverse reactions have been reported 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.

Hematologic Reactions: Thrombocytopenia [see Warnings and Precautions ]

Hypersensitivity reactions: Anaphylaxis, angioneurotic edema [see Warnings and Precautions]

Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis.

Skin reactions: cutaneous vasculitis, erythema multiforme



REPORTS OF SUSPECTED HUMIRA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Humira. The information is not vetted and should not be considered as verified clinical evidence.

Possible Humira side effects / adverse reactions in 58 year old male

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 58 year old male

Reactions: Arthralgia, Cerebrovascular Accident

Suspect drug(s):
Humira
    Indication: Psoriatic Arthropathy

Humira
    Indication: Psoriasis
    Start date: 2008-01-01

Other drugs received by patient: Captopril; Lisinopril; Metoprolol Tartrate; Aspirin; Lisinopril; Welchol



Possible Humira side effects / adverse reactions in 39 year old female

Reported by a health professional (non-physician/pharmacist) from Norway on 2011-10-03

Patient: 39 year old female

Reactions: Salivary Gland Cancer

Adverse event resulted in: death

Suspect drug(s):
Enbrel
    Dosage: 50 mg, weekly
    Indication: Rheumatoid Arthritis
    Start date: 2001-04-23
    End date: 2005-03-16

Humira
    Dosage: 40 mg every second week
    Indication: Rheumatoid Arthritis
    Start date: 2005-03-16
    End date: 2006-03-06

Other drugs received by patient: Methotrexat /00113801/; Humalog



Possible Humira side effects / adverse reactions in 60 year old male

Reported by a physician from France on 2011-10-03

Patient: 60 year old male

Reactions: Cerebrovascular Accident

Adverse event resulted in: hospitalization

Suspect drug(s):
Humira



See index of all Humira side effect reports >>

Drug label data at the top of this Page last updated: 2007-10-01

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