Instructions for Humira solution for injection 40 mg/0.4 ml syringe complete with wipes No. 2
Composition
active substance: adalimumab;
1 pre-filled single-dose syringe contains 40 mg of adalimumab in 0.4 mL of solution;
Excipients: mannitol (E 421), polysorbate-80, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: colorless aqueous solution from clear to opalescent, practically free from foreign impurities.
Pharmacotherapeutic group
Immunosuppressants. Tumor necrosis factor-alpha inhibitors. Adalimumab.
Pharmacological properties
Humira® (adalimumab) is a recombinant human immunoglobulin (IgG1), a monoclonal antibody containing only human peptide sequences. Humira® was produced by phage display technology, which resulted in human-specific heavy and light chain variable regions that exhibit specificity for tumor necrosis factor (TNF), as well as human IgG1 heavy chain and kappa-type light chain sequence. Humira® binds with high affinity and specificity to soluble TNF-alpha, but not to lymphotoxin (TNF-beta). Humira® is produced by recombinant DNA technology in a mammalian cell expression system. It consists of 1,300 amino acids and has a molecular weight of approximately 148 kilodaltons.
Adalimumab specifically binds to TNF and neutralizes the biological effects of TNF by blocking its interaction with the p55 and p75 TNF receptors on the cell surface. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated levels of TNF are found in the synovial fluid of patients with rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). TNF plays an important role in the pathological inflammation and destruction of joint tissue that is characteristic of these diseases. Elevated levels of TNF are also found in psoriatic plaques. The use of Humira® in patients with plaque psoriasis can reduce epidermal thickening and inflammatory cell infiltration. The relationship between these pharmacodynamic effects and the mechanism(s) by which Humira® exerts its clinical efficacy is unknown.
Adalimumab also modulates biological responses induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 at IC50 1–2 × 10-10 M).
Pharmacodynamics.
In patients with RA, Humira® caused a rapid reduction from baseline in acute phase inflammatory markers (C-reactive protein (CRP), serum cytokines (IL-6) and erythrocyte sedimentation rate). Reductions in CRP levels were also observed in patients with JRA, Crohn's disease, ulcerative colitis and hidradenitis suppurativa, along with significant reductions in TNF-alpha and inflammatory markers such as human leukocyte antigen (HLA-DR) and myeloperoxidase (MPO) in the colon of patients with Crohn's disease. Serum levels of matrix metalloproteinases (MMP-1 and MMP-3), which are involved in tissue remodeling that underlies cartilage destruction, were also reduced. Mild to moderate anemia and lymphocytopenia, as well as increased neutrophil and platelet counts, are common in patients with RA, PsA, and AS. These hematological markers of chronic inflammation are commonly improved with Humira®.
Pharmacokinetics. Absorption and distribution
Following a single subcutaneous dose of 40 mg Humira®, the absorption and distribution of adalimumab were slow, with mean peak serum concentrations occurring approximately 5 days after administration. The mean absolute bioavailability of adalimumab, calculated in three studies, following a single 40 mg subcutaneous dose was 64%.
After a single intravenous dose of 0.25 to 10 mg/kg, concentrations were dose proportional. After a dose of 0.5 mg/kg (approximately 40 mg), clearance ranged from 11 to 15 mL/h, volume of distribution (Vss) was 5 to 6 L, and the mean terminal half-life was approximately 2 weeks. Synovial fluid concentrations of adalimumab in RA patients ranged from 31 to 96% of serum levels.
Following subcutaneous administration of Humira® 40 mg every other week in patients with RA, steady-state concentrations ranged from 5 mcg/mL (without concomitant methotrexate) to 8-9 mcg/mL (with methotrexate). Steady-state serum adalimumab concentrations increased approximately proportionally with subcutaneous doses of 20, 40, and 80 mg every other week or weekly.
In children with polyarticular JRA aged 2–4 years and in children aged 4 years and older weighing less than 15 kg, the mean steady-state concentrations after administration of Humira® 24 mg/m2 with methotrexate were 7.9 ± 5.6 μg/mL (101% CV).
Following subcutaneous administration of Humira® at a dose of 24 mg/m2 (maximum 40 mg) every 2 weeks to patients aged 6 to 17 years with enthesitis-related arthritis, steady-state concentrations (measured at week 24) were 8.8 ± 6.6 μg/mL without concomitant methotrexate and 11.8 ± 4.3 μg/mL with methotrexate.
In adult patients with psoriasis, the mean steady-state concentration was 5 μg/mL during monotherapy with adalimumab 40 mg every 2 weeks.
Following subcutaneous administration of Humira® at a dose of 0.8 mg/kg (maximum 40 mg) every 2 weeks to children with chronic plaque psoriasis, steady-state concentrations were approximately 7.4 ± 5.8 μg/mL (79% CV).
In patients with hidradenitis suppurativa, after administration of Humira® 160 mg at week 0 followed by 80 mg at week 2, serum concentrations were approximately 7 to 8 mcg/mL at weeks 2 and 4. Mean steady-state concentrations from week 12 to week 36 were approximately 8 to 10 mcg/mL when Humira® was administered at a dose of 40 mg every week.
The effect of adalimumab in adolescents with hidradenitis suppurativa was determined using pharmacokinetic modeling and simulation based on pharmacokinetics in other pediatric indications (plaque psoriasis, juvenile rheumatoid (idiopathic) arthritis (JRA), Crohn's disease (CD) and enthesitis-related arthritis). The recommended dose regimen for adolescents with hidradenitis suppurativa is 40 mg every 2 weeks. Since the effect of adalimumab may be weight-dependent, the recommended adult dose of 40 mg once weekly may be used in adolescents with high body weight and inadequate response to treatment.
In patients with Crohn's disease, after administration of Humira® 80 mg at week 0 followed by 40 mg at week 2, the serum concentration was approximately 5.5 mcg/mL during induction therapy. After administration of Humira® 160 mg at week 0 followed by 80 mg at week 2, the serum concentration was approximately 12 mcg/mL during induction therapy. The mean steady-state concentration was approximately 7 mcg/mL during Humira® maintenance dose of 40 mg every other week.
In children with moderately to severely active Crohn's disease, the initial dose of Humira® in the open-label study was 160/80 mg or 80/40 mg at weeks 0 and 2, based on body weight. At week 4, patients were randomized 1:1 to receive either the standard dose (40/20 mg every other week) or the low dose (20/10 mg every other week) for maintenance therapy, based on body weight. The mean steady-state concentration was approximately 15.7 ± 6.6 μg/mL at week 4 in patients weighing 40 kg or more (160/80 mg) and 10.6 ± 6.1 μg/mL in patients weighing less than 40 kg (80/40 kg).
In patients with ulcerative colitis, following an initial dose of 160 mg Humira at week 0 followed by 80 mg at week 2, the serum concentration was approximately 12 mcg/mL during induction therapy. The mean steady-state concentration was approximately 8 mcg/mL during Humira maintenance dose of 40 mg every other week.
In children with ulcerative colitis, the mean steady-state serum adalimumab concentration at week 52 following subcutaneous administration of a weight-based dose of 0.6 mg/kg (maximum 40 mg) every other week was 5.01 ± 3.28 μg/mL. In patients receiving a dose of 0.6 mg/kg (maximum 40 mg) every other week, the mean (± standard deviation) steady-state serum adalimumab concentration at week 52 was 15.7 ± 5.60 μg/mL. In patients with uveitis, following administration of Humira® at an initial dose of 80 mg at week 0 followed by 40 mg every other week starting at week 1, the mean steady-state concentration was approximately 8 to 10 μg/mL.
Based on population pharmacokinetic and pharmacokinetic/pharmacodynamic modeling and simulation, adalimumab exposure and efficacy are comparable in patients receiving 80 mg every 2 weeks and in patients receiving 40 mg weekly (including adult patients with rheumatoid arthritis, hidradenitis suppurativa, ulcerative colitis, Crohn's disease or plaque psoriasis, adolescent patients with hidradenitis suppurativa, and children weighing ≥ 40 kg with ulcerative colitis and Crohn's disease).
There are no clinical data on the effect of the starting dose of adalimumab on the condition of children under 6 years of age. It is predicted that in the absence of methotrexate, the starting dose may increase the systemic exposure of adalimumab.
Breeding
A population pharmacokinetic analysis of data from over 1300 patients with RA showed a trend for the apparent clearance of adalimumab to increase with increasing body weight. After adjusting for differences in body weight, gender and age were found to have minimal effects on adalimumab clearance. Serum levels of free adalimumab (not bound to anti-adalimumab antibodies (AAA)) were lower in patients with AAA. Humira® has not been studied in patients with hepatic or renal impairment.
The safety and efficacy of Humira® in children for indications other than those listed in the “Indications” section have not been established.
Indication
Rheumatoid arthritis (RA)
Humira® in combination with methotrexate is indicated for:
treatment of moderately to severely active rheumatoid arthritis in adult patients who have not had an adequate response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate;
Treatment of active, progressive, highly active rheumatoid arthritis in adult patients who have not previously received methotrexate therapy.
Humira® can be used as monotherapy in cases of intolerance to methotrexate or when continued methotrexate therapy is unacceptable.
Humira® has been shown to inhibit the progression of structural joint damage as confirmed by radiography and improve functional status when used concomitantly with methotrexate.
Psoriatic arthritis (PsA)
Humira® is indicated for the treatment of active and progressive psoriatic arthritis in adult patients who have had an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). Humira® has been shown to slow the rate of progression of peripheral joint damage as measured by radiographic imaging in patients with symmetrical polyarticular disease and improve functional status.
Axial spondyloarthritis Ankylosing spondylitis (AS)
Humira® is indicated for the treatment of adult patients with highly active ankylosing spondylitis who have not responded to conventional therapy.
Axial spondyloarthritis without radiographic evidence of AS
Humira® is indicated for the treatment of adult patients with highly active axial spondyloarthritis without radiographic evidence of AS, but with evidence of inflammation as determined by elevated CRP levels and/or MRI (magnetic resonance imaging).
Crohn's disease (CD)
Humira® is indicated for the treatment of moderately to severely active Crohn's disease in adult patients who have failed to respond to a full course of therapy with corticosteroids and/or immunosuppressants, or who are intolerant to or have medical contraindications to such therapies.
Ulcerative colitis (UC)
Humira® is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy, including corticosteroids and/or 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications to such therapies.
Plaque psoriasis (PP)
Humira® is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who require systemic therapy.
Hidradenitis suppurativa (HS)
Humira® is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adult patients who have failed to respond to conventional systemic therapy.
Uveitis
Humira® is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adult patients who have failed corticosteroid therapy, who require a reduction in the dose of corticosteroids, or who are intolerant to or have medical contraindications to corticosteroid therapy.
In pediatrics Juvenile rheumatoid (idiopathic) arthritis (JRA) Polyarticular juvenile rheumatoid (idiopathic) arthritis
Humira® in combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis in children aged 2 years and older who have had an inadequate response to therapy with one or more disease-modifying antirheumatic drugs (DMARDs).
Humira® can be used as monotherapy in patients who are intolerant to methotrexate or when continued methotrexate therapy is inappropriate. Humira® has not been studied in patients under 2 years of age.
Enthesitis-associated arthritis
Humira® is indicated for the treatment of active enthesitis-related arthritis in children aged 6 years and older who have failed to respond to conventional therapy, or who are intolerant to or have medical contraindications to such therapies.
Crohn's disease (CD) in children
Humira® is indicated for the treatment of moderately to severely active Crohn's disease in children aged 6 years and older who have failed to respond to conventional therapy, including initial nutritional therapy, corticosteroids and/or immunomodulators, or who are intolerant to or have medical contraindications to such therapies.
Plaque psoriasis (PP) in children
Humira® is indicated for the treatment of severe chronic plaque psoriasis in children aged 4 years and older who have not responded to, or who are intolerant to, topical therapy or phototherapy.
Hidradenitis suppurativa (HS) in adolescents
Humira® is indicated for the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adolescents aged 12 years and older who have not responded to conventional systemic HH therapy.
Humira® is indicated for the treatment of chronic non-infectious anterior uveitis in children aged 2 years and older who have failed to respond to or are intolerant to conventional therapy, or for whom conventional therapy is contraindicated.
Ulcerative colitis in children
Humira® is indicated for the treatment of moderately to severely active ulcerative colitis in children aged 6 years and older who have had an inadequate response to conventional therapy, including corticosteroids and/or 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications to such therapies.
Contraindication
Hypersensitivity to adalimumab or to any other component of the drug.
Active tuberculosis or other severe infections such as sepsis and opportunistic infections (see section "Special warnings and precautions for use").
Moderate and severe heart failure (NYHA class III/IV) (see section "Special warnings and precautions for use").
Interaction with other medicinal products and other types of interactions
Humira® has been studied in patients with RA, JRA and PsA, treated as monotherapy and concomitantly with methotrexate. Antibody formation was lower when Humira® was co-administered with methotrexate compared to monotherapy. Administration of Humira® without methotrexate resulted in increased antibody formation, increased clearance and reduced efficacy of adalimumab (see section 5.2).
The concomitant use of Humira® with anakinra is not recommended (see section “Special precautions for use. Concomitant use with DMARDS or TNF antagonists”).
The concomitant use of Humira® with abatacept is not recommended (see section “Special precautions for use. Concomitant use with DMARDS or TNF antagonists”).
Application features
Tracking capability
In order to improve control of the use of biological drugs, it is necessary to clearly record the trade name and batch number of the administered drug.
Infections
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may increase the risk of developing infections. Therefore, patients should be closely monitored for infections, including tuberculosis, before, during, and after treatment with Humira®. Since the elimination of adalimumab may take up to four months, monitoring should continue during this period.
Humira® should not be used in patients with active infections, including chronic or localized infections, until the infection is controlled. In patients who have been exposed to a patient with tuberculosis or have returned from countries with a high incidence of tuberculosis or from areas endemic for mycoses such as histoplasmosis, coccidioidomycosis or blastomycosis, the benefit/risk ratio should be assessed before initiating Humira® (see “Other opportunistic infections” below).
Patients who develop a new infection while receiving Humira should be carefully evaluated and monitored. Treatment should be discontinued if a severe infection or sepsis develops and appropriate antimicrobial or antifungal therapy should be administered until the infection is controlled. Physicians should exercise caution when considering the use of Humira in patients with a history of recurrent infections or underlying conditions (including concomitant immunosuppressive therapy) that may predispose patients to infections.
Severe infections
Serious infections, including sepsis, caused by bacterial, mycobacterial, invasive fungal, parasitic, viral or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients receiving Humira®.
Other serious infections identified during clinical trials include pneumonia, pyelonephritis, septic arthritis, and septicemia. Hospitalization or fatalities associated with infections have been reported.
Tuberculosis
Cases of reactivation and the development of new tuberculosis infection, including pulmonary and non-pulmonary forms (i.e. disseminated tuberculosis), have been reported in patients treated with Humira®.
Humira® therapy should not be administered if active tuberculosis is diagnosed (see section “Contraindications”).
In all situations described below, the benefit/risk ratio of therapy should be assessed very carefully.
If latent tuberculosis is suspected, you should consult a doctor who has experience in treating tuberculosis.
If latent tuberculosis is diagnosed, specific anti-tuberculosis prophylaxis treatment should be administered before initiating Humira® therapy in accordance with local recommendations.
Anti-tuberculosis treatment should be considered before initiating Humira therapy in patients with risk factors for tuberculosis infection but who have tested negative for latent tuberculosis, and in patients with a history of latent or active tuberculosis for whom appropriate treatment cannot be confirmed.
Despite prophylactic anti-tuberculosis treatment, cases of reactivation of tuberculosis have occurred in patients receiving Humira®. Some patients who had previously successfully treated active tuberculosis have experienced re-development of tuberculosis while receiving Humira®.
All patients should be advised to seek medical advice if they develop symptoms suggestive of tuberculosis (e.g. persistent cough, weight loss, low-grade fever, listlessness) during or after treatment with Humira®.
Other opportunistic infections
Opportunistic infections, including invasive fungal infections, have been reported during Humira therapy. These infections have sometimes been missed in patients receiving TNF-antagonists, resulting in delayed initiation of appropriate treatment and sometimes fatal outcomes.
Patients taking TNF blockers are at increased risk of developing serious fungal infections such as histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, etc. Humira® therapy should be discontinued immediately if a patient develops fever, malaise, weight loss, increased sweating, cough, dyspnea, and/or pulmonary infiltrates or other signs of serious systemic illness (with or without shock), and an invasive fungal infection should be suspected. The decision to use empirical antifungal therapy in such patients should be made in consultation with a specialist in the diagnosis and treatment of invasive fungal infections.
Hepatitis B reactivation
Cases of hepatitis B reactivation have occurred in patients taking TNF-blockers who were chronic carriers of hepatitis B virus (HBV), i.e. in whom the surface antigen of the virus was detected. Some cases have been fatal. Patients should be tested for HBV infection before starting treatment with Humira®. Patients who test positive for HBV infection are advised to consult a physician experienced in the management of hepatitis B.
HBV carriers who require treatment with Humira® should be closely monitored for signs and symptoms of active HBV infection during therapy and for several months after discontinuation. There are no adequate data on the treatment of HBV carriers with antiviral agents in combination with TNF antagonists to prevent HBV reactivation. Patients who develop HBV reactivation should discontinue Humira® and initiate effective antiviral therapy with appropriate supportive care.
Neurological disorders
There have been isolated reports of new onset or exacerbation of clinical symptoms and/or radiographic signs of central nervous system demyelinating disorders, including multiple sclerosis, optic neuritis, and peripheral nervous system demyelinating disorders, including Guillain-Barré syndrome, with the use of TNF-blockers, including Humira®. Prescribers should exercise caution when prescribing Humira® to patients with a history of or recent onset of central or peripheral demyelinating disorders; Humira® therapy should be discontinued if these disorders occur. There is a known association between intermediate uveitis and central nervous system demyelinating disorders. Neurological evaluation should be performed in patients with non-infectious intermediate uveitis prior to initiating Humira therapy and periodically during therapy to assess for the development of pre-existing or newly occurring central nervous system demyelinating disorders.
Allergic reactions
Serious allergic reactions, including anaphylaxis, have been reported following administration of Humira®. If an anaphylactic reaction or other serious allergic reaction occurs, Humira® should be discontinued immediately and appropriate therapy should be initiated.
Immunosuppression
In clinical studies of Humira® in 64 patients with RA, there were no cases of suppression of delayed-type hypersensitivity, decreased immunoglobulin levels, or quantitative changes in effector T and B cells, as well as NK cells, monocytes/macrophages, and neutrophils.
Malignant neoplasms and lymphoproliferative diseases
In controlled clinical trials of TNF blockers, malignancies, including lymphoma, have been reported more frequently in patients treated with TNF blockers than in control patients. However, this was rare. In the post-marketing period, cases of leukemia have been reported in patients treated with TNF antagonists. There is an increased background risk of lymphoma and leukemia in patients with long-standing rheumatoid arthritis and highly active inflammatory process, which makes risk assessment difficult. The data available to date do not allow us to exclude the risk of lymphoma, leukemia, and other malignancies in patients treated with TNF antagonists.
In the post-marketing period, isolated cases of malignancies, sometimes fatal, have been reported in children, adolescents and young adults (up to 22 years of age) treated with TNF-blockers (initiation of therapy ≤ 18 years of age), including adalimumab. In approximately half of these cases, the malignancies were lymphomas. The remaining cases were of various types of malignancies, including those usually associated with immunosuppression. The risk of malignancies in children and adolescents receiving TNF-antagonists cannot be excluded.
In the post-marketing period, hepatosplenic T-cell lymphoma has been reported very rarely in patients receiving adalimumab. This rare type of lymphoma is characterized by a very aggressive course and is usually fatal. Some of these cases of hepatosplenic T-cell lymphoma with Humira® have occurred in young adult patients receiving concomitant therapy with azathioprine or 6-mercaptopurine for the treatment of inflammatory bowel disease. The potential risk of concomitant use of azathioprine or 6-mercaptopurine with Humira® should be carefully evaluated. The risk of hepatosplenic T-cell lymphoma in patients receiving Humira® cannot be excluded (see section 4.8).
Humira® has not been studied in patients with a history of malignancy or in patients who develop malignancy who continue Humira® therapy. This should be taken into account and caution should be exercised when prescribing Humira® to such patients (see section 4.8).
All patients, especially those with a history of extensive immunosuppressive therapy and patients with psoriasis who have received PUVA therapy, should be evaluated for non-melanoma skin cancer before and during treatment with Humira. Melanoma and Merkel cell carcinoma have also been reported in patients treated with TNF-antagonists, including adalimumab (see section 4.8).
In an exploratory clinical trial evaluating another TNF blocker (infliximab), patients with moderate to severe chronic obstructive pulmonary disease (COPD) reported a higher incidence of neoplasms, mostly in the lungs, head, and neck, compared with controls. All patients were long-term smokers. Therefore, caution should be exercised when using any TNF blocker in patients with chronic obstructive pulmonary disease and in patients at increased risk of neoplasms due to smoking.
Hematological disorders Pancytopenia, including aplastic anemia, has been reported rarely with TNF-blockers. Hematological adverse reactions, including clinically significant cytopenia (e.g., thrombocytopenia, leukopenia), have been reported with Humira®. All patients should be advised to seek immediate medical attention if symptoms suggestive of a blood disorder (such as persistent fever, bruising, bleeding, pale skin and mucous membranes) develop while taking Humira®. Discontinuation of Humira® should be considered if a patient develops a serious blood disorder. Vaccination
In a study of 226 adult patients with rheumatoid arthritis treated with adalimumab or placebo, similar humoral responses were obtained to standard 23-valent pneumococcal vaccine and trivalent influenza vaccine. There are no data on secondary transmission in patients receiving live vaccines and Humira®.
For pediatric patients, it is recommended that all required vaccinations be completed, if possible, according to the schedule prior to initiating therapy with Humira®.
Administration of live vaccines (e.g. BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months after the mother's last adalimumab injection during pregnancy.
Chronic heart failure (CHF)
In clinical trials with another TNF blocker, worsening of CHF and increased CHF-related mortality were reported. Cases of worsening CHF have also been reported in patients receiving Humira® therapy. Humira® should be used with caution in patients with mild heart failure (NYHA class I/II). Humira® is contraindicated in patients with moderate to severe CHF (see section 4.8). Humira® should be discontinued if the patient develops new or worsening symptoms of chronic heart failure.
Autoimmune processes
Treatment with Humira® may induce the development of autoantibodies. The effect of long-term use of Humira® on the development of autoimmune diseases is unknown. If symptoms suggestive of lupus-like syndrome occur after initiation of Humira® therapy and positive double-stranded DNA antibody tests are detected, Humira® should be discontinued.
Concomitant use with biological DMARDs or TNF antagonists
Serious infections have been observed in clinical trials of concomitant use of anakinra and another TNF antagonist, etanercept, which did not provide a therapeutic advantage over etanercept alone. Given the nature of the adverse events observed with the combination of etanercept and anakinra, similar toxicities may occur with the combination of anakinra and another TNF blocker. Therefore, the combination of adalimumab and anakinra is not recommended.
Concomitant use of adalimumab with other biologic DMARDs (e.g. anakinra and abatacept) or with other TNF antagonists is not recommended due to the possible increased risk of infections and other potential pharmacological interactions (see section 4.5).
Surgical interventions
Limited safety data are available for surgical procedures in patients receiving Humira®. The long half-life of adalimumab should be considered if surgery is planned. Patients undergoing surgery and receiving Humira® should be carefully monitored for infections and appropriate measures taken. Limited safety data are available for patients undergoing arthroplasty while receiving Humira®.
Small bowel obstruction
Failure to respond to treatment for Crohn's disease may indicate the presence of a fixed fibrotic stricture that requires surgical treatment. Available data suggest
