Cimzia 200 mg solution for injection in pre-filled syringe

  • Name:

    Cimzia 200 mg solution for injection in pre-filled syringe

  • Company:
    info
  • Active Ingredients:

    Certolizumab Pegol

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

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Summary of Product Characteristics last updated on medicines.ie: 26/7/2019

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UCB (Pharma) Ireland Limited

UCB (Pharma) Ireland Limited

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1 - 0 of 27 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 1 August 2019 Ed-Both

Reasons for updating

  • Add New Doc

Updated on 26 July 2019 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.1 & 5.1: 

- additional description added

In section 4.8:

- additional clinical study data added

- additional description added

In section 5.2:

- additional clinical study data added

Updated on 20 March 2019 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 20 March 2019 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 7 September 2018 PIL

Reasons for updating

  • Change to section 5 - how to store or dispose

Updated on 7 September 2018 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

6.3     Shelf life

18 months.2 years.

See also section 6.4 for shelf-life related to storage at room temperature up to a maximum of 25°C.

 

6.4     Special precautions for storage

 

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The pre-filled syringes may be stored at room temperature (up to 25°C) for a single period of maximum 10 days with protection from light. At the end of this period the pre-filled syringes must be used or discarded.

Updated on 15 June 2018 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

-‘’Plaque psoriasis” information has been added in the following sections ‘’ 4.1 Therapeutic indications’’,’’ 4.2 Posology and method of administration’’, ‘’ 4.8 Undesirable effects”, 5.1 Pharmacodynamic properties’’;
-‘’Posology’’ and ‘’Latex-sensitivity’’ information has also been updated in section ’’ 4.2 Posology and method of administration’’;
-‘’Rheumatoid arthritis”, ‘’Tabulated list of adverse reactions”, ‘’Description of selected adverse reactions-Infections, Malignancies and lymphoproliferative disorders” has been updated in section ‘’4.8 Undesirable effects”;
-‘’Maintenance of response”, ‘’Quality of life / Patient reported outcomes”,’’Immunogenicity” has been updated in section ‘’5.1 Pharmacodynamic properties’’;
-‘’Distribution’’, ’’Pharmacokinetic/pharmacodynamic relationship” has been updated in section’’ 5.2 Pharmacokinetic properties’’;

- The section “6.5 Nature and contents of container’’ has been updated;
-‘’Section 10. DATE OF REVISION OF THE TEXT’’ has been updated {MM/YYYY} 06/2018.

Updated on 15 June 2018 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - how to take/use
  • Change to date of revision

Updated on 18 January 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 18 January 2018 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.6 Fertility, Pregnancy and lactation updated regarding women of childbearing age.$0$0$0$04.6 Fertility, Pregnancy and lactation$0$0$0$0$0Women of childbearing potential$0$0Women of childbearing potential should use adequate contraception to prevent pregnancy and continue its use for at least 5 months after the last Cimzia administration.$0$0The use of adequate contraception should be considered for women of childbearing potential. For women planning pregnancy, continued contraception may be considered for 5 months after the last Cimzia dose due to its elimination rate (see section 5.2), but the need for treatment of the woman should also be taken into account (see below).$0$0$0$0$0Pregnancy$0$0There are no adequate data from the use of Cimzia in pregnant women.$0$0Data from more than 500 prospectively collected pregnancies exposed to Cimzia with known pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, does not indicate a malformative effect of Cimzia. However, the available clinical experience is too limited to, with a reasonable certainty,conclude that there is no increased risk associated with Cimzia administration during pregnancy.$0$0Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn.$0$0$0$0$0Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn. Therefore, Cimzia is not recommended during pregnancy.$0$0$0$0$0Cimzia should only be used during pregnancy if clinically needed.$0$0$0$0$0Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab-fragment of certolizumab pegol (no Fc region) (see section 5.3). $0$0$0$0$0Limited clinical data show low levels of certolizumab pegol in plasma of an infant born by a treated woman. Consequently, these infants may be at increased risk for infection. Administration of live vaccines to infants exposed to certolizumab pegol in utero is not recommended for a minimum of 5 months following the mother’s last Cimzia administration during pregnancy (see section 4.4).$0$0$0$0$0In a clinical study 16 women were treated with certolizumab pegol (200 mg every 2 weeks or 400 mg every 4 weeks) during pregnancy. Certolizumab pegol plasma concentrations measured in 14 infants at birth were Below the Limit of Quantification (BLQ) in 13 samples; one was 0.042 µg/ml with an infant/mother plasma ratio at birth of 0,.09%. At Week 4 and Week 8, all infant concentrations were BLQ. The clinical significance of low levels certolizumab pegol for infants is unknown. It is recommended to wait a minimum of 5 months following the mother’s last Cimzia administration during pregnancy before administration of live or live-attenuated vaccines (e.g. BCG vaccine), unless the benefit of the vaccination clearly outweighs the theoretical risk of administration of live or live-attenuated vaccines to the infants.$0$0$0$0$0Breastfeeding$0$0There is insufficient information on the excretion of certolizumab pegol in human or animal breast milk. Since immunoglobulins are excreted into human breast milk, a risk to the breastfeeding child cannot be excluded. A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with Cimzia should be made taking into account the benefit of breastfeeding to the child and the benefit of Cimzia therapy to the woman.$0$0In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol from plasma to breast milk was observed. The percentage of the maternal certolizumab pegol dose that  reaching an infant during a 24 hour period was estimated to 0.04% to 0.30 %. In addition, since certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, the absolute bioavailability is expected to be very low in a breastfed infant.$0$0Consequently, Cimzia can be used during breastfeeding.$0$0$0$0$0Fertility$0$0Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been observed with no apparent effect on fertility (see section 5.3). $0

Updated on 17 January 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 17 January 2018 PIL

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 6 - date of revision

Updated on 22 May 2017 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes in section: 4.2 and 5.1.

Updated on 19 May 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to information for healthcare professionals

Updated on 6 January 2017 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SmPC changes: in sections 4.8 and 5.1: to add information about the long-term data, following the submission of two final study reports.

 

 

Updated on 20 December 2016 PIL

Reasons for updating

  • Change to other sources of information section

Updated on 22 September 2016 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition of 'in pre-filled syringe' in the section 1 of the SmPC.

Updated on 21 September 2016 PIL

Reasons for updating

  • Change to date of revision
  • Change to appearance of the medicine
  • Change to dosage and administration

Updated on 18 December 2015 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

The following sections have been updated: 

 

Section 4.1: to add a new indication.

Section 5.1. to add new results of clinical trials.

Updated on 17 December 2015 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 23 June 2015 SmPC

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 5.1 Pharmacodynamic properties: the Immunogenicity sub-section has been updated.

 

Updated on 2 February 2015 SmPC

Reasons for updating

  • Change to product name
  • Change to section 1 - Name of medicinal product

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 1 - in pre-filled syringe removed from product name.

Updated on 30 January 2015 PIL

Reasons for updating

  • Change of trade or active ingredient name

Updated on 8 January 2015 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 - updated warning for tuberculosis
Section 4.8 - clarification on viral infections and tuberculosis as adverse events

Updated on 7 January 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 11 November 2014 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - MA number
  • Change to section 9 - Date of renewal of authorisation

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company


1. NAME OF THE MEDICINAL PRODUCT

Cimzia 200 mg solution for injection in pre filled syringe

4.8 Undesirable effects

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

6.5 Nature and contents of container

One ml pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber), containing 200 mg of certolizumab pegol.

Pack size of 2 syringes and 2 alcohol wipes.
Multipack containing 6 (3 packs of 2) pre-filled syringes and 6 (3 packs of 2) alcohol wipes.
Multipack containing 10 (5 packs of 2) pre filled syringes and 10 (5 packs of 2) alcohol wipes.
Pack size of 2 pre-filled syringes with needle guard and 2 alcohol wipes (for use by healthcare professionals only).

Not all pack sizes may be marketed.


8. MARKETING AUTHORISATION NUMBER(S)

EU/1/09/544/004

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 01 October 2009
Date of latest renewal: 16 May 2014

Updated on 10 June 2014 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 6.5 - Nature and contents of container
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 The following are the main changes, all other changes are minor.


3.       PHARMACEUTICAL form

 

Solution for injection (injection).

 

 

4.1     Therapeutic indications

 

Psoriatic arthritis

The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to Week 24 was 11.7% in the Phase III placebo-controlled trial in patients with psoriatic arthritis. Antibody formation was associated with lowered drug plasma concentration.

 

 

6.5         Nature and contents of container

 

One ml pre-filled syringe (type I glass) with a plunger stopper (bromobutyl rubber), containing 200 mg of certolizumab pegol.

 

 

 

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation: 01 October 2009

Date of latest renewal: 16 May 2014

 

 

10.     DATE OF REVISION OF THE TEXT

 

05/2014

Updated on 10 June 2014 PIL

Reasons for updating

  • Change to packaging
  • Change to warnings or special precautions for use
  • Change to side-effects
  • Addition of information on reporting a side effect.

Updated on 10 January 2014 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to instructions about missed dose
  • Change to instructions about overdose
  • Change to side-effects

Updated on 18 December 2013 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 4.1 Therapeutic indications 
Axial spondyloarthritis

Cimzia is indicated for the treatment of adult patients with severe active axial spondyloarthritis, comprising:

Ankylosing spondylitis (AS)

Adults with severe active ankylosing spondylitis who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

Axial spondyloarthritis without radiographic evidence of AS

Adults with severe active axial spondyloarthritis without radiographic evidence of AS but with objective signs of inflammation by elevated CRP and /or MRI, who have had an inadequate response to, or are intolerant to NSAIDs.

 

Psoriatic arthritis

Cimzia, in combination with MTX, is indicated for the treatment of active psoriatic arthritis in adults when the response to previous DMARD therapy has been inadequate.

Cimzia can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.

For details on therapeutic effects, see section 5.1.

 
4.2 Posology and method of administration

Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of conditions for which Cimzia is indicated. Patients should be given the special alert card.

 

Posology

Loading dose

The recommended starting dose of Cimzia for adult patients is 400 mg (given as 2 subcutaneous injections of 200 mg each) at weeks 0, 2 and 4. For rheumatoid arthritis and psoriatic arthritis, MTX should be continued during treatment with Cimzia where appropriate.

 

Maintenance dose

Rheumatoid arthritis

After the starting dose, the recommended maintenance dose of Cimzia for adult patients with rheumatoid arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative maintenance dosing of 400 mg every 4 weeks can be considered. MTX should be continued during treatment with Cimzia where appropriate.

 

Axial spondyloarthritis

After the starting dose, the recommended maintenance dose of Cimzia for adults patients with axial spondyloarthritis is 200 mg every 2 weeks or 400 mg every 4 weeks.

 

Psoriatic arthritis

After the starting dose, the recommended maintenance dose of Cimzia for adult patients with psoriatic arthritis is 200 mg every 2 weeks. Once clinical response is confirmed, an alternative maintenance dosing of 400 mg every 4 weeks can be considered. MTX should be continued during treatment with Cimzia where appropriate.

For the above indications, available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks of treatment.

 

Missed dose

Patients who miss a dose should be advised to inject the next dose of Cimzia as soon as they remember and then continue injecting subsequent doses as originally instructed.

 

 4.8 Undesirable effects

Axial spondyloarthritis

Cimzia was studied in 325 patients with active axial spondyloarthritis in a placebo-controlled clinical trial (AS001) for up to 30 months. The safety profile for axial spondyloarthritis patients treated with Cimzia was consistent with the safety profile in rheumatoid arthritis and previous experience with Cimzia.

Psoriatic arthritis

Cimzia was studied in 409 patients with psoriatic arthritis in a placebo-controlled clinical trial (PsA001) for up to 30 months. The safety profile for psoriatic arthritis patients treated with Cimzia was consistent with the safety profile in rheumatoid arthritis and previous experience with Cimzia.

 

Malignancies and lymphoproliferative disorders

One case of lymphoma was also observed in the Phase III psoriatic arthritis clinical trial.

 

Creatine phosphokinase elevations

The frequency of creatine phosphokinase (CPK) elevations was generally higher in patients with axSpA as compared to the RA population. The frequency was increased both in patients treated with placebo (2.8% vs 0.4% in axSpA and RA populations, respectively) as well as in patients treated with Cimzia (4.7% vs 0.8% in axSpA and RA populations, respectively). The CPK elevations in the axSpA study were mostly mild to moderate, transient in nature and of unknown clinical significance with no cases leading to withdrawal.

 

Reporting of suspected adverse reactions

Healthcare professionals are asked to report any suspected adverse reactions via IMB and MHRA (refer to SmPC for further details)

 
5.1 Pharmacodynamic properties

DoseFlex clinical trial:

The efficacy and safety of 2 dose regimens (200 mg every 2 weeks and 400 mg every 4 weeks) of Cimzia versus placebo were assessed in an 18-week, open-label, run-in, and 16-week randomised, double-blind, placebo‑controlled clinical trial in adult patients with active rheumatoid arthritis diagnosed according to the ACR criteria who had inadequate response to MTX.

 

Patients received loading doses of Cimzia 400 mg at weeks 0, 2, and 4 followed by Cimzia 200 mg every 2 weeks during the initial open label period. Responders (achieved ACR 20) at week 16 were randomised at week 18 to Cimzia 200 mg every 2 weeks, Cimzia 400 mg every 4 weeks, or placebo in combination with MTX for an additional 16 weeks (total trial length: 34 weeks). These 3 groups were well balanced with regards to clinical response following the active run-in period (ACR 20: 83-84% at week 18).

 

The primary endpoint of the study was the ACR 20 responder rate at week 34. The results at week 34 are shown in Table 5. Both Cimzia regimens showed sustained clinical response and were statistically significant compared to placebo at week 34. The ACR 20 endpoint was achieved for both Cimzia 200 mg every 2 weeks and 400 mg every 4 weeks.

 

Table: 5 ACR response in DoseFlex clinical trial at week 34 (refer to SmPC for further details)

Axial spondyloarthritis

The efficacy and safety of Cimzia were assessed in one multicenter, randomized, double-blind, placebo-controlled trial (AS001) in 325 patients ≥18 years of age with adult-onset active axial spondyloarthritis for at least 3 months as defined by the Assessment of Spondyloarthritis International Society (ASAS) Classification Criteria for axial spondyloarthritis. The axial spondyloarthritis overall population included subpopulations with and without (non-radiographic axial spondyloarthritis (nr-axSpA)) radiographic evidence for ankylosing spondylitis (AS).  Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, spinal pain ≥ 4 on a 0 to 10 Numerical Rating Scale (NRS) and increased CRP or current evidence of sacroiliitis on Magnetic Resonance Imaging (MRI).Patients must have been intolerant to or had an inadequate response to at least one NSAID. Overall 16% of patients had prior TNF-antagonist exposure. Patients were treated with a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of Cimzia every 2 weeks or 400 mg of Cimzia every 4  weeks or placebo. 87.7% of patients received concomitant NSAIDs.The primary efficacy endpoint was the ASAS20 response rate at Week 12.

 

Key efficacy outcomes

In AS001 clinical trial, at Week 12 ASAS20 responses were achieved by 58% of patients receiving Cimzia 200 mg every 2 weeks and 64% of patients receiving Cimzia 400 mg every 4 weeks as compared to 38% of patients receiving placebo (p < 0.01). In the overall population, the percentage of ASAS20 responders was clinically relevant and significantly higher for the Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks treatment groups compared to placebo group at every visit from Week 1 through Week 24 (p≤0.001 at each visit). At Weeks 12 and 24, the percentage of subjects with an ASAS40 response was greater in the Cimzia-treated groups compared to placebo.

 

Similar results were achieved in both the ankylosing spondylitis and non-radiographic axial spondyloarthritis subpopulations. In women, ASAS20 responses were not statistically significantly different from placebo until after the Week 12 time point.

 

Improvements in ASAS 5/6, Partial Remission and BASDAI-50 were statistically signficant at Week 12 and Week 24 and were sustained up to Week 48 in the overall popualtion as well as in the subpopulations.  Key efficacy outcomes from the AS001 clinical trial are shown in Table 5.

 

Table: 5 Key efficacy outcomes in AS001 clinical trial (percent of patients) (refer to SmPC for further details)

 

Spinal Mobility

Spinal mobility was assessed by BASMI at Baseline, Week 12 and Week 24. Clinically meaningful and statistically significant differences in Cimzia-treated patients compared with placebo-treated patients were demonstrated at each post-baseline visit.  The difference from placebo tended to be greater in nr-axSpA than in the AS subpopulation which  may be due to less chronic structural damage in nr-axSpA patients.

 

Physical function response and health-related outcomes

In the AS001 clinical trial, Cimzia-treated patients reported significant improvements in physical function as assessed by the BASFI and in pain as assessed by the Total and Nocturnal Back Pain NRS scales as compared to placebo. Cimzia-treated patients reported significant improvements in tiredness (fatigue) as reported by the BASDAI-fatigue item and in health-related quality of life as measured by the ankylosing spondylitis QOL (ASQoL) and the SF-36 Physical and Mental Component Summaries and all domain scores as compared to placebo. Cimzia-treated patients reported significant improvements in axial spondyloarthritis-related productivity at work and within household, as reported by the Work Productivity Survey as compared to placebo. These improvements were sustained up to Week 48.

 

Inhibition of inflammation in Magnetic Resonance imaging (MRI)

In an imaging sub-study including 153 patients, signs of inflammation were assessed by MRI at week 12 and expressed as change from baseline in SPARCC (Spondyloarthritis Research Consortium of Canada) score for sacroiliac joints and ASspiMRI-a score in the Berlin modifications for the spine. Significant inhibition of inflammatory signs in both sacroiliac joints and the spine was observed in the Cimzia-treated patient (all doses group), in the overall axial spondyloarthritis population as well as in the sub-populations of ankylosing spondylitis and non-radiographic axial spondyloarthritis.

 

Psoriatic arthritis

The efficacy and safety of Cimzia were assessed in a multicentre, randomised, double-blind, placebo controlled clinical trial (PsA001) in 409 patients ≥18 years of age with adult-onset active psoriatic arthritis for at least 6 months as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria. Patients had ≥ 3 swollen and tender joints and increased acute phase reactants. Patients also had active psoriatic skin lesions or a documented history of psoriasis and had failed 1 or more DMARDs. Previous treatment with one TNF-antagonist was allowed and 20% of patients had prior TNF-antagonist exposure. Patients received a loading dose of Cimzia 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either Cimzia 200 mg every 2 weeks or 400 mg every 4 weeks or placebo every 2 weeks. Patients receiving concomitant NSAIDs and conventional  DMARDs were 72.6% and 70.2% respectively. The two primary endpoints were the percentage of patients achieving ACR20 response at Week 12 and change from baseline in modified Total Sharp Score (mTSS) at Week 24. Efficacy and safety of Cimzia in patients with PsA whose predominant symptoms were sacroiliitis or axial spondyloarthritis have not been separately analysed.

 

ACR response

Cimzia-treated patients had a statistically significant higher ACR20 response rate at Week 12 and Week 24 compared with placebo-treated patients (p<0.001). The percentage of ACR20 responders was clinically relevant for the Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks treatment groups compared to placebo group at every visit after baseline through Week 24 (nominal p≤0.001 at each visit). At week 12 and 24 improvements in parameters of peripheral activity characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, dactylitis and enthesitis) were seen in the Cimzia-treated patients (nominal p-value p<0.01). Among 273 patients initially randomised to Cimzia 200 mg every 2 weeks and Cimzia 400 mg every 4 weeks, 237 (86.8%) were still on this treatment at Week 48.  Of the 138 patients randomised to Cimzia 200 mg every 2 weeks, 92, 68 and 48 had an ACR 20/50/70 response, respectively. Of the 135 patients randomised to Cimzia 400 mg every 4 weeks, 89, 62 and 41 patients had an ACR 20/50/70 response, respectively. Cimzia treated patients also had significant improvements in ACR50 and 70 response rates.  Key efficacy outcomes from the PsA001 clinical trial are shown in Table 7.

 

Table: 7 Key efficacy outcomes in PsA001 clinical trial (percent of patients) (refer to SmPC for further details)

 

Radiographic response

In PsA001 clinical trial, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified total Sharp score (mTSS) and its components, the Erosion Score (ES) and Joint Space Narrowing score (JSN) at Week 24, compared to baseline. The mTSS Score was modified for psoriatic arthritis by addition of hand distal interphalangeal joints. Cimzia treatment inhibited the radiographic progression compared with placebo treatment at Week 24 as measured by change from baseline in total mTSS Score (LS mean [±SE] score was 0.28 [±0.07] in the placebo group compared with 0.06 [± 0.06] in the Cimzia all doses group; p=0.007). Inhibition of radiographic progression was maintained with Cimzia treatment up to Week  48 in the subset of patients at higher risk of radiographic progression (patients with a Baseline mTSS score of > 6).

 

Physical function response and health-related outcomes

In PsA001 clinical trial, Cimzia-treated patients reported significant improvements in physical function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI), in pain as assessed by the Patient Assessment of Arthritis Pain (PAAP) and in tiredness (fatigue) as reported by the Fatigue Assessment Scale (FAS) as compared to placebo. Cimzia-treated patients reported significant improvements in health-related quality of life as measured by the psoriatic arthritis QoL (PsAQoL) and the SF-36 Physical and Mental Components and in psoriatic arthritis-related productivity at work and within household, as reported by the Work Productivity Survey compared to placebo. These improvements were sustained up to Week 48.

 

Immunogenicity

Axial spondyloarthritis

The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to Week 24 was 4.4% in the phase III placebo controlled trial in patients with axial spondyloarthritis. Antibody formation was associated with lowered drug plasma concentration.

 

Psoriatic arthritis

The overall percentage of patients with antibodies to Cimzia detectable on at least one occasion up to Week 24 was 11.7% in the Phase III placebo-controlled trial in patients with psoriatic arthritis. Antibody formation was associated with lowered drug plasma concentration. The number of patients with antibodies to Cimzia in this trial was insufficient to make valid assessment of the impact of the antibody formation on efficacy.

Updated on 21 October 2013 SmPC

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Minor typos

Updated on 29 August 2013 SmPC

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 4.2       Posology and method of administration

Method of administration

After proper training in injection technique, patients may self-inject using the pre-filled syringe if their physician determines that it is appropriate and with medical follow-up as necessary. The pre-filled syringe with needle guard should only be used by healthcare professionals.

4.8       Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

6.5       Nature and contents of container

Pack size of 2 pre-filled syringes with needle guard and 2 alcohol wipes (for use by healthcare professionals only).

Updated on 5 June 2013 PIL

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  • Change to side-effects

Updated on 30 April 2013 SmPC

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4.4     Special warnings and precautions for use

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), have been reported in patients treated with TNF-antagonists. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. The majority of reported TNF-antagonist cases occurred in adolescent and young adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine concomitantly with a TNF-antagonist at or prior to diagnosis. A risk for development of hepatosplenic T-cell lymphoma in patients treated with Cimzia cannot be excluded.

 

 

4.8         Undesirable effects

Cimzia was studied in 4,049 patients with rheumatoid arthritis in controlled and open label trials for up to 92 months. The data in Table 1 are based primarily on the placebo controlled Studies involving 2,965 patients receiving Cimzia and 1,137 patients receiving placebo during the controlled period.

 

The proportion of patients who discontinued treatment due to adverse events during the controlled trials was 4.4% for patients treated with Cimzia and 2.7% for patients treated with placebo.

 

The most common adverse reactions belonged to the system organ classes Infections and infestations, reported in 14.4% of patients on Cimzia and 8.0% of patients on placebo, General disorders and administration site conditions, reported in 8.8% of patients on Cimzia and 7.4% of patients on placebo, and Skin and subcutaneous tissue disorders, reported in 7.0% of patients on Cimzia and 2.4% of patients on placebo.

 

Table :1.          Adverse drug reactions in clinical trials and postmarketing

System Organ Class                 Frequency        Adverse Drug Reactions

Ear and labyrinth disorders          Uncommon      tinnitus, vertigo


Infections

The incidence rate of new cases of infections in placebo-controlled clinical trials in rheumatoid arthritis was 1.03 per patient-year for all Cimzia-treated patients and 0.92 per patient-year for placebo-treated patients. The infections consisted primarily of upper respiratory tract infections, urinary tract infections, and lower respiratory tract infections and herpes viral infections (see sections 4.3 and 4.4).

 

In the placebo-controlled clinical trials, there were more new cases of serious infection in the Cimzia treatment groups (0.07 per patient-year; all doses), compared with placebo (0.02 per patient-year). The most frequent serious infections included pneumonia, tuberculosis infections. Serious infections also included invasive opportunistic infections (e.g. pneumocystosis, fungal oesophagitis, nocardiosis and herpes zoster disseminated). There is no evidence of an increased risk of infections with continued exposure over time (see section 4.4).

 

Malignancies and lymphoproliferative disorders

Excluding non-melanoma of the skin, 121 malignancies including 5 cases of lymphoma were observed in the Cimzia RA clinical trials in which a total of 4,049 patients were treated, representing 9,277 patient-years. Cases of lymphoma occurred at an incidence rate of 0.05 per 100 patient-years and melanoma at an incidence rate of 0.08 per 100 patient-years with Cimzia in rheumatoid arthritis clinical trials (see section 4.4).

 

Autoimmunity

In the pivotal studies, for subjects who were ANA negative at baseline, 16.7% of those treated with Cimzia developed positive ANA titers, compared with 12.0% of subjects in the placebo group. For subjects who were anti-dsDNA antibody negative at baseline, 2.2% of those treated with Cimzia developed positive anti-dsDNA antibody titers, compared with 1.0% of subjects in the placebo group. In both placebo-controlled and open-label follow-up clinical trials for rheumatoid arthritis, cases of lupus-like syndrome were reported uncommonly. There have been rare reports of other immune-mediated conditions; the causal relationship to Cimzia is not known. The impact of long-term treatment with Cimzia on the development of autoimmune diseases is unknown.

 

Injection site reactions

In the placebo-controlled rheumatoid arthritis clinical trials, 5.8% of patients treated with Cimzia developed injection site reactions such as erythema, itching, haematoma, pain, swelling or bruising, compared to 4.8% of patients receiving placebo. Injection site pain was observed in 1.5% of patients treated with Cimzia with no cases leading to withdrawal.

 

 

5.1     Pharmacodynamic properties

Immunogenicity

The overall percentage of patients with antibodies to Cimzia detectable on at least 1 occasion was 9.6% in RA placebo-controlled trials. Approximately one-third of antibody-positive patients had antibodies with neutralising activity in vitro. Patients treated with concomitant immunosuppressants (MTX) had a lower rate of antibody development than patients not taking immunosuppressants at baseline. Antibody formation was associated with lowered drug plasma concentration and in some patients, reduced efficacy.

 

Updated on 9 April 2013 PIL

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  • Change to warnings or special precautions for use

Updated on 8 April 2013 SmPC

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Section 4.4
Skin cancers
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF antagonists including certolizumab pegol (see section 4.8). Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer.

Section 4.8

Neoplasms benign, malignant and unspecified (including cysts and polyps)
Not known: Merkel cell carcinoma* 


Updated on 4 March 2013 SmPC

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4.4     Special warnings and precautions for use

 

 

Hypersensitivity

Severe hypersensitivity reactions have been reported rarely following Cimzia administration. Some of these reactions occurred after the first administration of Cimzia. If severe reactions occur, administration of Cimzia should be discontinued immediately and appropriate therapy instituted.

 

Updated on 16 October 2012 PIL

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Updated on 25 July 2012 SmPC

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4.4     Special warnings and precautions for use

 

Infections

Physicians should exercise caution when considering the use of Cimzia in patients with a history of recurring or opportunistic infection or with underlying conditions which may predispose patients to infections, including the use of concomitant immunosuppressive medications.

 

Vaccinations

Patients treated with Cimzia may receive vaccinations, except for live vaccines. No data are available on the response to live vaccinations or the secondary transmission of infection by live vaccines in patients receiving Cimzia. Live vaccines should not be administered concurrently with Cimzia.

In a placebo-controlled clinical trial in patients with rheumatoid arthritis, similar antibody response between Cimzia and placebo treatment were observed when the pneumococcal polysaccharide vaccine and influenza vaccine were administered concurrently with Cimzia. Patients receiving Cimzia and concomitant methotrexate had a lower humoral response compared with patients receiving Cimzia alone. The clinical significance of this is unknown.

 

Pregnancy

Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn. Therefore, Cimzia is not recommended during pregnancy.

Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab-fragment of certolizumab pegol (no Fc region) (see section 5.3). Limited clinical data show low levels of certolizumab pegol in plasma of an infant born by a treated woman. Consequently, these infants may be at increased risk for infection. Administration of live vaccines to infants exposed to certolizumab pegol in utero is not recommended for a minimum of 5 months following the mother’s last Cimzia administration during pregnancy (see section 4.4).

 

In a clinical trial to assess the effect of Cimzia on semen quality parameters, 20 healthy male subjects were randomized to receive a single subcutaneous dose of 400 mg of Cimzia or placebo. During the 14-week follow-up, no treatment effects of Cimzia were seen on semen quality parameters compared to placebo.

 

4.8         Undesirable effects

 

Gastrointestinal disorders Common nausea

 

5.3     Preclinical safety data

 

Distribution studies have demonstrated that placental and milk transfer of cTN3 PF to the foetal and neonatal circulation is negligible. Data from a human closed-circuit placental transfer model in vitro suggest low or negligible transfer to the foetal compartment (see section 4.6).

Updated on 3 February 2012 PIL

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Updated on 25 November 2011 SmPC

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Hepatitis B Virus (HBV) reactivation

Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including Cimzia, who are chronic carriers of this virus (i.e., surface antigen positive)Reactivation of HBV has occurred in patients who are chronic carriers of this virus receiving TNF antagonists. Some cases have had a fatal outcome.

 

Patients should be tested for HBV infection before initiating treatment with Cimzia. For patients who test positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended.As HBV infection has also been reported with Cimzia, patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating Cimzia therapy. Adequate data on treating patients who are carriers of HBV with TNF antagonist therapy, in conjunction with anti-viral therapy, to prevent HBV reactivation are not available.

 

Carriers of HBV who require treatment with TNF antagonistsCimzia should be closely monitored for signs and symptomsclinical and laboratory signs of active HBV infection throughout therapy and for 5 several months following termination of therapy, especially if the patient is on concomitant corticosteroid therapy. Adequate data of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, Cimzia should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.

Updated on 26 May 2011 PIL

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Updated on 23 February 2011 SmPC

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Update of section 4.8 of the SmPC following assessment of PSUR 1

Updated on 26 October 2010 SmPC

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None provided

Updated on 22 October 2010 PIL

Reasons for updating

  • New PIL for new product