abbvie logoPrescribing information and adverse event reporting information can be found at the bottom of this page.This promotional website has been organised and funded by AbbVie.AXHUR161078(4). Date of preparation: June 2017

HUMIRA is the first and only biologic licensed for adult non-infectious uveitis;

intermediate, posterior and panuveitis.1

HUMIRA is NOW FUNDED through NHS England for severe refractory uveitis.*2
* Interim Clinical Commissioning Policy Number 170010/PS
For full start criteria click here

The First and Only Biologic 2,3 Option for Adult Non-Infectious Uveitis

HUMIRA is the first and only biologic to gain control over adult non-infectious intermediate, posterior and panuveitis.

HUMIRA is a fully human monoclonal antibody that specifically targets TNF-α, a cytokine with a key role in inflammation and disease progression in uveitis.TNF-α can break down the blood-retinal barrier, resulting in potential retinal damage and reduced vision.1,3

Ophthalmologists are advised to consult with an appropriate specialist before initiation of treatment with HUMIRA.1

HUMIRA is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate.1

Patient funding criteria (interim commissioning policy)2

All patients fulfilling the following criteria should be referred to a specialised ophthalmology service with tertiary care facilities for inflammatory ocular diseases.

Start Criteria from interim policy
Adults eligible for the use of HUMIRA for the treatment of non-infectious uveitis; intermediate, posterior and panuveitis and in whom corticosteoroids are inadequate/inappropriate would need to meet the following criteria:

EITHER

  • Failure to achieve an oral prednisolone dose of <10mg daily despite failing (due to inefficacy or intolerance) prior treatment with two conventional second-line immunosuppressive agents for a minimum of 3 months (eg, mycophenolate mofetil, tacrolimus, methotrexate, cyclosporine A, azathioprine) with evidence of worsening visual function.
    • Worsening visual function is defined as either a reduction in visual acuity by ≥5 logMAR letters (0.1 log units), or worsening peripheral vision (quantified by Humphrey, Goldmann or Octopus perimetry) [A logMAR (logarithm of the Minimal Angle of Resolution) chart comprises rows of letters and is used to estimate visual acuity. It is more accurate than the Snellen chart, which has traditionally been used by GPs and optometrists. It is the preferred assessment tool in research studies.]
OR

  • Severe immediately sight-threatening uveitis at risk of permanent loss of vision despite treatment with ≥1.5g intravenous methyl prednisolone (in divided doses over 3 days) or 1mg/kg oral prednisolone for 1 week, defined as one or more of the following criteria:
    • Reduction of visual acuity by ≥15 logMAR letters (0.3 log units)
    • Vasculitis within the retinal vascular arcades
    • Standardisation of Uveitis Nomenclature (SUN) vitreous haze score of ≥2
    • Central macular thickness >400um

Patients must be registered with NHS England’s standard electronic contractual prior approval system confirming the start criteria are met.

In treatment
Response to therapy should be assessed after 3 months of therapy and 6 months of therapy and thereafter re-assessed every 6 months whilst treatment continues. The following data points must be collected for each patient at these visits:

  • Visual acuity measured in LogMAR
  • Visual field scored as stable, worse or improved based on Humphrey, Goldmann or Octopus perimetry
  • SUN anterior chamber activity and vitreous haze score
  • Daily oral prednisolone dose
  • Daily dose of conventional second-line immunosuppressive agents
  • Frequency of topical steroid eye drops
  • Intraocular pressure
  • Frequency of topical antihypertensive drops
  • Central macular thickness

Adults who respond to treatment with HUMIRA will continue treatment for 18 months at which time a trial of treatment withdrawal will be undertaken. If relapse occurs, restarting HUMIRA will be considered using the start criteria stated in the policy (see above).

Response to treatment with HUMIRA is defined as achieving one or more of the following criteria:

  • Reduction in daily oral prednisolone dose by 5mg, or to ≤10mg
  • Reduction in conventional second-line immunosuppressive treatment
  • For eyes with impaired visual acuity, an improvement in visual acuity by ≥5 LogMAR letters (0.1 log units)
  • For eyes with reduced visual field, an improvement in visual field based on an assessment using Humphrey, Goldmann or Octopus perimetry
  • For eyes with increased central macular thickness, a ≥10% reduction in central macular thickness

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AbbVie on .


Stop criteria
HUMIRA for the treatment of uveitis is stopped using following criteria:

  1. Failure to achieve the response criteria defined above after 3 months of treatment
  2. Adverse reaction to HUMIRA

Please read the full interim commissioning policy NHSE 170010/PS

Dosing

Humira self-administered subcutaneous dosing for at-home convenience:

Recommended dosing for adults with non-infectious intermediate, posterior and panuveitis:1

  • An initial dose of 80mg, followed by 40mg given every other week (EOW) starting one week after the initial dose
  • Treatment with HUMIRA can be initiated in combination with corticosteroids and/or other non-biologic immunomodulatory agents
  • Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with HUMIRA

It is recommended that the benefit and risk of continued long-term treatment should be evaluated on a yearly basis.

After appropriate training with injection technique.

Humira Efficacy

VISUAL 1 trial 4

Study design:
A 80-week phase 3, randomised, double-masked, placebo-controlled, multi centre clinical trial in 223 adult patients with non-infectious intermediate, posterior, or panuveitis uncontrolled (active) disease.

Patients were enrolled at 67 study sites located in Australia, Canada, Europe, Israel, Latin America, and the United States.

Endpoint:
The primary endpoint was time to Treatment Failure (TF) in ≥1 eye, defined as ≥1 of the following:

  • New, active, inflammatory chorioretinal or vascular lesions;
  • Worsening of BCVA by ≥15 letters at or after week 6;
  • Inability to achieve ≤0.5+ AC cell grade or ≤0.5+ VH grade (at week 6); or
  • 2-step increase in AC cell grade or VH grade (after week 6)

Patient population:
Patients entered the study with uncontrolled (active) disease at baseline, despite oral corticosteroids (10-60mg per day for ≥2 weeks).

Active disease was defined as one or more of the following:

  • Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
  • ≥2+ anterior chamber (AC) cells (SUN criteria)
  • ≥2+ vitreous haze (VH) (National Eye Institute [NEI]/SUN criteria)

At study entry, patients could be also taking one concomitant non-biologic immunosuppressant (methotrexate, cyclosporine, mycophenolate mofetil, azathioprine and tacrolimus) at pre-defined, stable doses.

Design:
Patients in both arms of the study received a 60mg prednisolone burst at baseline, which was tapered according to a fixed schedule and discontinued by Week 15.

  • All patients using a topical steroid at baseline underwent a mandatory taper schedule from weeks 1 to 9

VISUAL 1 patients were randomised to receive placebo or HUMIRA until week 80.
HUMIRA (subcutaneous administration) dosing was as follows: Initial dose of 80mg, followed by 40mg given every other week (EOW) starting 1 week after initial dose.

Study results:
In VISUAL 1, HUMIRA met its primary endpoint by prolonging the time to TF by 85%§ vs. placebo (24 weeks vs. 13 weeks, p<0.001).

HUMIRA delivered early and sustained efficacy vs. placebo (figure 1).

Figure 1: Treatment failure on or after week 6. Adapted from Jaffe GJ et al., 2016.4

In VISUAL 1, patients on HUMIRA had a significantly lower risk for TF vs. placebo (HR=0.5; 95% CI 0.36-0.70; p<0.001).

Statistically significant differences in favour of HUMIRA vs. placebo were observed for each component of treatment failure: vitreous haze (p<0.001), new lesions (p=0.001), anterior chamber cells (p=0.01) and best corrected visual acuity (p=0.04).

§ 24 weeks/13 weeks = 1.846 (184.6%), therefore 24 weeks is 85% longer than 13 weeks.


VISUAL 2 trial 5

Study design:
A 80-week phase 3, randomised, double-masked, placebo-controlled, multi centre clinical trial in 229 adult patients with non-infectious intermediate, posterior, or panuveitis inactive, corticosteroid-dependent disease.

Patients were enrolled at 62 study sites from 21 countries.

Endpoint:
The primary endpoint was time to TF assessed from week 2 in ≥1 eye, defined as ≥1 of the following vs. baseline:

  • New, active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions
  • 2-step increase in AC cell grade
  • 2-step increase in VH cell grade
  • Worsening of BCVA by ≥15 letters

Patient population:
Patients entered the study with controlled (inactive) disease, but were unable to discontinue corticosteroids without experiencing a uveitic flare.

  • Before study entry, patients were taking oral corticosteroids (10-35mg)
  • Patients had a history of at least 1 disease flare within 18 months of the screening visit

Uveitic flare (active disease) was defined as one or more of the following:

  • Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
  • ≥2+ anterior chamber (AC) cells (SUN criteria)
  • ≥2+ vitreous haze (VH) (National Eye Institute [NEI]/SUN criteria)
  • Worsening of BCVA by ≥15 letters

At study entry, 47% of patients were taking a concomitant non-biologic immunosuppressant at pre-defined, stable doses (n=107/226).

‡ Azathioprine (6%), cyclosporine (12%), methotrexate (15%), or mycophenolate mofetil or equivalent (15%).

Design:
Prednisolone was tapered from week 2 for patients in both arms of the study according to dose and discontinued by week 19.

Study results:
In VISUAL 2, HUMIRA met its primary endpoint by prolonging treatment failure vs. placebo (median not estimable) [>80 weeks] vs. 36 weeks (8.3 months) (p=0.004).

HUMIRA delivered early and sustained efficacy vs. placebo (figure 2).

Figure 2: Treatment failure on or after week 2. Adapted from Nguyen QD et al., 2016.5

The superior efficacy of HUMIRA vs. placebo was seen as early as week 2 and was sustained throughout the entire 80-week study.

In VISUAL 2, patients on HUMIRA had a significantly lower risk for TF vs. placebo (HR=0.57; 95% CI 0.39-0.84; p=0.004).

For the individual components of TF, visual acuity was statistically significant vs. placebo.

All other components were not statistically significant.

Tolerability and Safety

The tolerability profiles in both the VISUAL 1 and VISUAL 2 trials were consistent with the known side-effect profile across the approved HUMIRA indications.1,4,5 Please click here to read the important safety information for HUMIRA.

Central nervous system (CNS) disorders: Prescribers should exercise caution in considering the use of HUMIRA in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of HUMIRA should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in patients with non-infectious intermediate uveitis prior to the initiation of HUMIRA therapy and regularly during treatment to assess for pre-existing or developing central demyelinating disorders.1

Patient Support Program

AbbVie provide a tailored patient support programme designed to support each patient’s treatment experience whilst on HUMIRA.

HUMIRA's heritage across indications

HUMIRA has experience with more than 23,000 patients in 71 clinical trials6, 19 years of experience7, and currently over 1,000,000 patients are treated worldwide with HUMIRA across 13 indications.8

HUMIRA has 13 approved indications.1

2003:

Moderate-to-Severe Rheumatoid Arthritis

2005:

Active and Progressive Psoriatic Arthritis

2006:

Severe Active Ankylosing Spondylitis

2007:

Moderate-to-Severe Chronic Plaque Psoriasis

Moderate-to-Severe Active Crohn’s Disease

2008:

Active Polyarticular Juvenile Idiopathic Arthritis (13–17 years, 2+ years from 2013)

2012:

Severe Non-Radiographic Axial Spondyloarthritis

Moderate-to-Severe Ulcerative Colitis

Severe Active Paediatric Crohn’s Disease (6–17 years)

2014:

Active Enthesitis-Related Arthritis (6+ years)

2015:

Severe Chronic Paediatric Plaque Psoriasis (4+ years)

Active, Moderate-to-Severe Hidradenitis Suppurativa

2016:

Non-Infectious Intermediate, Posterior and Panuveitis

Moderate-to-Severe Active Paediatric Crohn’s Disease (6-17 years)

HUMIRA is the first and only biologic licensed for adult non-infectious uveitis;

intermediate, posterior and panuveitis.1

Abbreviations:

AC
anterior chamber
BCVA
best corrected visual aculty
CI
confidence interval
CNS
central nervous system
EOW
every other week
HR
hazard ratio
ITT
intent to treat
MHRA
Medicines and Healthcare products Regulatory Agency
NEI
National Eye Institute
NICE
National Institute for Health and Care Excellence
SC
subcutaneous
SUN
Standardisation of Uveltis Nomenclature
TF
treatment failure
TNF
tumour necrosis factor
VH
vitreous haze

References:

  1. HUMIRA 40mg/0.4ml Summary of Product Characteristics. AbbVie Ltd.
    Available at www.medicines.org.uk/emc.
  2. NHS England. Interim Clinical Commissioning Policy Statement: Adalimumab for Severe Refractory Uveitis. Reference: NHS England 170010/PS
  3. Horai R, Caspi RR. J Interferon Cytokine Res 2011; 31(10): 733-744.
  4. Jaffe GJ et al., N Eng J Med 2016;375:932-43
  5. Nguyen QD et al., Lancet 2016; 388(10050):1183-1192.
  6. Burmester GR et al. Ann Rheum Dis 2013; 72(4): 517–24.
  7. Burmester GR et al. Ann Rheum Dis 2009; 68(12): 1863–9.
  8. AbbVie Ltd. Data on file RM17315.
 

Important safety information for HUMIRA:
You are also strongly advised to read the prescribing information (PI) which can be found at the end of this page.

  • Do not use Humira in active TB, opportunistic or other severe infections, moderate to severe heart failure (NYHA III/IV) or known hypersensitivity to any of the components of Humira.
  • Before initiation of Humira, evaluate all patients for infection, including active and latent TB, hepatitis B or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis.
  • Patients must be actively and regularly monitored for infections during and for 4 months after treatment with Humira and undergo a complete diagnostic evaluation.
  • Neurologic evaluation should be performed in patients with with non-infectious intermediate uveitis prior to the initiation of therapy and regularly during treatment to assess for pre-existing or developing central demyelinating disorders.
  • Patients should also be evaluated for non-melanoma skin cancer prior to and during Humira therapy
  • Other precautions also exist (please read the prescribing information).
  • Serious, including fatal, side effects have been reported including infections/sepsis (particularly in patients over 65), opportunistic infections, TB, endemic mycoses, intestinal perforation, demyelinating disease, malignancies including lymphoma (including hepatosplenic T cell lymphoma), leukaemia and skin cancers, reactivation of hepatitis B, hepatitis, liver failure, cytopenias, worsening heart failure, myocardial infarction, pulmonary embolism, pleural effusion, pulmonary fibrosis, cerebrovascular accident, interstitial lung disease, Stevens-Johnson syndrome, angioedema, anaphylaxis, sarcoidosis and worsening of symptoms of dermatomyositis.
AXHUR161078(4). Date of preparation: June 2017

Prescribing Information
Humira (adalimumab) 40 mg solution for injection in pre-filled pen or pre-filled syringe or paediatric vial containing 40 mg solution for injection. Refer to Summary of Product Characteristics (SmPC) for full information. Presentation: Each single dose pre-filled pen (0.4 ml), pre-filled syringe (0.4 ml) or vial (0.8 ml) contains 40 mg of adalimumab. Indications: Rheumatoid arthritis (RA), adults: In combination with methotrexate (MTX) for moderate to severe, active RA with inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX. In combination with MTX for severe, active and progressive RA when not previously treated with MTX. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Reduces rate of progression of joint damage on X-ray and improves physical function, in combination with MTX. Polyarticular juvenile idiopathic arthritis (pJIA), paediatrics 2 years and above: In combination with MTX, for active pJIA with inadequate response to one or more DMARDs; or monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Enthesitisrelated arthritis (ERA), paediatrics 6 years and above: For active ERA with inadequate response or intolerance to conventional therapy. Ankylosing spondylitis (AS), adults: For severe active AS with inadequate response to conventional therapy. Axial spondyloarthritis without radiographic evidence of AS (nr-axSpA), adults: For severe nr-axSpA with objective signs of inflammation (elevated CRP and/or MRI), and an inadequate response to or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Psoriatic arthritis (PsA), adults: For active and progressive PsA with inadequate response to DMARDs. Reduces rate of progression of peripheral joint damage on X-ray in polyarticular symmetrical subtypes of the disease and improves physical function. Psoriasis, adults: For moderate to severe chronic plaque psoriasis who are candidates for systemic therapy. Psoriasis, paediatrics 4 years and above: For severe chronic plaque psoriasis with inadequate response, or if topical therapy and phototherapies are inappropriate. Hidradenitis suppurativa (HS), adults and adolescents from 12 years of age: For active moderate to severe hidradenitis suppurativa (acne inversa) in patients with an inadequate response to conventional systemic HS therapy. Crohn’s disease (CD), adults: For moderately to severely active CD with inadequate response, contraindication or intolerance to corticosteroid and/or an immunosuppressant therapy. Crohn’s disease (CD), paediatrics 6 years and above: For moderately to severely active CD with inadequate response, contraindication or intolerance to conventional therapy including primary nutrition therapy and a corticosteroid, and/or an immunomodulator. Ulcerative colitis (UC), adults: For moderately to severely active UC with inadequate response, contraindication or intolerance to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA). Uveitis, adults: For the treatment of non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate. Dosage and administration: A specialist physician experienced in diagnosis and treatment of the indicated condition, to initiate and supervise treatment. Provide patients with special alert card. Patients may self-inject after proper injection training, with physician approval and appropriate medical follow-up. Optimise other concomitant therapies. RA, adults: 40 mg dose every other week. Concomitant MTX should be continued. During monotherapy, patients may require 40 mg each week if they have experienced a decrease in clinical response. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Consider need for dose interruption, e.g. before surgery or if serious infection occurs. Reintroduction after 70 day dose interruption gave same magnitudes of clinical response and similar safety profile as before dose interruption. pJIA, paediatrics 2 years and above: Treatment beyond 12 weeks reconsidered if no clinical response in that time. pJIA, paediatrics 2-<4 years: 24 mg/m2 body surface area up to 20 mg maximum single dose every other week (see vial SmPC for height/ weight dosing chart). pJIA, paediatrics 4-12 years: 24 mg/m2 body surface area up to 40 mg maximum single dose every other week (see vial SmPC for height/weight dosing chart). pJIA, paediatrics 13 years and above: 40 mg every other week regardless of body surface area. ERA, paediatrics 6 years and above: 24 mg/m2 body surface area up to 40 mg maximum single dose every other week (see SmPC for height/weight dosing chart). AS, nr-axSpA and PsA, adults: 40 mg every other week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Psoriasis, adults: 80 mg induction dose at week 0, 40 mg every other week from week 1. Treatment beyond 16 weeks should be reconsidered if no clinical response in that time. Beyond 16 weeks, patients with inadequate response can increase dosing frequency to 40 mg every week. If adequate response is achieved with an increased dosing frequency, the dose may subsequently be reduced to 40 mg every other week. If there is inadequate response to the increased frequency, carefully reconsider treatment. Psoriasis, paediatrics 4 years and above: 0.8 mg/kg body weight (maximum 40 mg/dose) weekly for the first 2 doses then every other week (see vial SmPC for weight dosing chart). Treatment beyond 16 weeks should be reconsidered if no response in that time. HS, adults: 160 mg initially at Day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later at Day 15 (given as two 40 mg injections in one day). Two weeks later (Day 29) continue with a dose of 40 mg every week. Antibiotics may be continued if necessary. Concomitant topical antiseptic wash on HS lesions should be used on a daily basis. Treatment beyond 12 weeks should be reconsidered in a patient with no improvement in that time. Reintroduction after interruption: 40 mg every week. Evaluate periodically the benefit and risk of continued long-term treatment. HS, adolescents from 12 years of age weighing at least 30 kg: 80 mg initially at week 0 (given as two 40 mg injections on day one). 40 mg injection in week 1 followed by 40 mg every other week. In adolescent patients with inadequate response to Humira 40 mg every other week an increase in dosing frequency to 40 mg every week may be considered. Antibiotics may be continued if necessary. Concomitant topical antiseptic wash on HS lesions should be used on a daily basis. If no improvement after 12 weeks refer to SmPC for guidance. CD, adults: Induction: 80 mg Week 0 and 40 mg at Week 2. For a more rapid response: 160 mg at Week 0 (either as 4 injections in 1 day or 2 injections/day for 2 consecutive days) and 80 mg at Week 2; risk of adverse events higher during induction. Maintenance: 40 mg every other week. If decrease in clinical response, can increase dose to 40 mg weekly. Corticosteroids may be tapered in maintenance phase in accordance with clinical guidelines. Patients with no response by Week 4 may benefit from continued therapy to Week 12. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. CD, paediatrics 6 years and above < 40 kg: Induction: 40 mg Week 0, 20 mg at Week 2. For a more rapid response: 80 mg Week 0 (2 injections in 1 day), 40 mg at Week 2; risk of adverse events higher during induction. Maintenance: 20 mg every other week. If insufficient response, consider 20 mg every week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. CD, paediatrics 6 years and above ≥ 40 kg: Induction: 80 mg Week 0, 40 mg at Week 2. For a more rapid response: 160 mg at Week 0 (4 injections in 1 day or 2 injections/day for 2 consecutive days), 80 mg at Week 2; risk of adverse events higher during induction. Maintenance: 40 mg every other week. If insufficient response, consider 40 mg every week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. UC, adults: Induction: 160 mg at Week 0 (as 4 injections in 1 day or 2 injections/day for 2 consecutive days) and 80 mg at Week 2. Maintenance: 40 mg every other week. During maintenance, corticosteroids may be tapered in accordance with clinical guidelines. If insufficient response, consider 40 mg every week. Treatment beyond 8 weeks should be reconsidered if no clinical response in that time. Uveitis, adults: 80mg induction dose at week 0, maintenance dose; 40 mg every other week starting at week 1. Treatment can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment with Humira. Contraindications: Active tuberculosis (TB), severe infections (e.g. sepsis), and opportunistic infections; moderate to severe heart failure (NYHA class III/IV); hypersensitivity to adalimumab or any excipients. Warnings and precautions: Clearly record trade name and batch number of administered product to improve traceability of biological products. Infections: Patients are more susceptible to serious infections especially if impaired lung function. Monitor for infections, including TB, before, during and for 4 months after treatment. Do not initiate treatment with an active infection, until it is controlled. Consider risk/benefit prior to treatment in patients exposed to high risk of TB or endemic mycoses. Evaluate new infections during treatment and monitor closely. Stop treatment if new serious infection or sepsis, and treat appropriately. Exercise caution in patients with a history of recurring infections or who are predisposed to infections. Serious infections: Serious infections, including those with hospitalisation or death, reported in patients receiving treatment. TB: Consult SmPC for details. Reactivation and new onset TB, both pulmonary and extra-pulmonary (disseminated) reported. Screen all patients before therapy initiation for active or latent TB. If latent TB suspected, consult physician with appropriate expertise and follow local treatment recommendations for prophylaxis prior to initiation of Humira. Despite prophylaxis, TB reactivation has occurred on Humira. If active TB is diagnosed, do not initiate treatment. Other opportunistic infections: Opportunistic infections observed in patients receiving Humira. Stop treatment in patients with signs and symptoms of such infections. Consult with physician with appropriate expertise for diagnosis and administration of empiric antifungal therapy in these patients. Hepatitis B reactivation: Reactivation has occurred in chronic carriers (surface antigen positive) tested for HBV infection before initiating treatment. HBV carriers should consult a specialist physician and be closely monitored for reactivation of HBV infection throughout therapy and for several months following termination of treatment. If reactivation occurs stop treatment and initiate appropriate anti-viral and supportive treatment. Neurological events: Caution in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders. Rare association with new onset or exacerbation of symptoms and/or radiographic evidence of central and peripheral demyelinating disease. Discontinuation of treatment should be considered if any of these disorders develop. Neurologic evaluation should be performed in patients with non-infectious intermediate uveitis prior to initiation of treatment and regularly during treatment, to assess for existing or developing central demyelinating disorders. Allergic reactions: Reports of serious allergic reactions including anaphylaxis received. For serious allergic or anaphylactic reaction stop Humira immediately and initiate appropriate therapy. Malignancies and lymphoproliferative disorders: A possible risk of malignancy, including lymphomas and leukaemia, in all patients, including paediatric patients, treated with TNF antagonists. Examine all patients, especially those with a medical history of extensive immunosuppressant or PUVA treatment, for non-melanoma skin cancer prior to and during treatment; caution in COPD patients, and in patients with increased risk for malignancy due to heavy smoking. Consider the potential risk with the combination of AZA or 6-MP and Humira (hepatosplenic T-cell lymphoma has occurred). Risk of hepatosplenic T-cell lymphoma cannot be excluded. Caution in patients with a history of malignancy. Risk of developing dysplasia or colon cancer is unknown. Patients with UC, history of dysplasia or colon carcinoma to be screened for dysplasia before and during treatment. Haematologic reactions: Adverse events of the haematologic system reported with Humira. Patients should seek immediate medical attention if signs and symptoms of blood dyscrasias. Vaccinations: Patients may receive concurrent vaccinations, except for live vaccines. Bring paediatric patients up to date with all immunisations prior to Humira treatment. Congestive heart failure: See contraindications. Caution is advised with mild heart failure (NYHA class I/II). Discontinue treatment for new or worsening symptoms of congestive heart failure. Autoimmune processes: Autoimmune antibodies may form. Stop treatment if development of a lupus-like syndrome with positive antibodies against double-stranded DNA. Surgery: Consider the long half-life of Humira for planned surgical procedures. Monitor for infections. Small bowel obstruction: Failure to respond to treatment for CD may indicate the presence of fixed fibrotic stricture requiring surgical treatment. Elderly patients: Serious infections were higher in patients over 65 years of age, some of whom had a fatal outcome. Consider risk of infections. Interactions: Combination of adalimumab with other biologic DMARDs (e.g. anakinra and abatacept) or other TNF-antagonists is not recommended. Fertility, pregnancy and lactation: Not recommended during pregnancy. Women of childbearing age to use adequate contraception, and continue its use for at least 5 months after the last treatment. Women must not breast feed for at least 5 months after the last treatment. Side effects: Very common ≥ 1/10: Infections, leucopaenia, anaemia, lipids increased, headache, abdominal pain, nausea and vomiting, elevated liver enzymes, rash (including exfoliative rash), musculoskeletal pain, injection site reaction. Common ≥ 1/100 to < 1/10: skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma), benign neoplasm, leucocytosis, thrombocytopaenia, hypersensitivity, allergies (including seasonal allergy), hypokalaemia, uric acid increased, blood sodium abnormal, hypocalcaemia, hyperglycaemia, hypophosphatemia, dehydration, mood alterations (including depression), anxiety, insomnia, paraesthesias, migraine, nerve root compression, visual impairment, conjunctivitis, blepharitis, eye swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, dyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux disease, sicca syndrome, worsening or new onset of psoriasis (including palmoplantar pustular psoriasis), urticaria, bruising (including purpura), dermatitis (including eczema), onychoclasis, hyperhidrosis, alopecia, pruritus, muscle spasms (including blood creatine phosphokinase increased), renal impairment, haematuria, chest pain, oedema, pyrexia, coagulation and bleeding disorders, autoantibody test positive, blood lactate dehydrogenase increased, impaired healing. Serious, including fatal, side effects have been reported including infections/sepsis, intestinal perforation, opportunistic infections, TB, endemic mycoses, demyelinating disease, malignancies including lymphoma, (including hepatosplenic T-cell lymphoma), leukaemia and skin cancer (including melanoma and Merkel cell carcinoma), cytopenias, worsening heart failure, myocardial infarction, pulmonary embolism, pleural effusion, pulmonary fibrosis, cerebrovascular accident, interstitial lung disease, Stevens-Johnson syndrome, angioedema, anaphylaxis, sarcoidosis, hepatitis, liver failure and worsening of symptoms of dermatomyositis. Other less common and rarely reported side effects are listed in the SmPC. Basic NHS price: £704.28 (for 2 pens or 2 syringes or 2 vials). Legal category: POM. Marketing Authorisation numbers: EU/1/03/256/001, EU/1/03/256/013, EU/1/03/256/017. Further information: available from AbbVie Ltd., Maidenhead, SL6 4UB, United Kingdom. Date of revision of PI: December 2016, PI/Humira(combined)/37
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AbbVie on