Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 02-Feb-2017

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·        Section 4.4 – Special warnings and precautions for use: the subsection ‘skin cancers’ has been updated to reflect the report of MCC in a golimumab clinical study.

• Section 4.8 – Undesirable effects

• : Change in frequency of Merkel cell carcinoma from not known to rare. Reference to MCC not being reported in golimumab clinical studies has been deleted.

Reasons for adding or updating:

• Change to section 6.3 - Shelf life
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 08-Dec-2016

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$0·Section 6.3 – Shelf life: The shelf lifehas been extended from 18 months to 22 months.$0

Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 13-Oct-2016

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$0·Section 4.8 –Undesirable effects integrated safety changes based on GO-AHEADstudy (P07642) results and PURSUIT$0$0· Section 5.1 – Pharmacodynamicproperties to update the safety and efficacy information with the databased on Week 60 P07642 (nr-axial SpA) results and the final report of PURSUIT(UC) study C0524T18$0$0·The SmPCs have been combined for the pre-filledpen and pre-filled syringe for 50 mg strength and for the pre-filled pen andpre-filled syringe for 100 mg strength respectively, in line with the latestQRD template version 9.1. $0

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Jun-2016

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Section 4.1 – Therapeutic indications: addition of Polyarticular juvenile idiopathic arthritis (pJIA).

Section 4.2 – Posology and method of administration: Dosage instructions for pJIA and clinical response information added.

Section 4.4 – Special warnings and precautions for use: Recommendation added to ensure Paediatric vaccinations are up to date prior to starting Simponi treatment.

Section 4.8 – Undesirable effects: Paragraph added regarding the phase III safety study in pJIA patients, the type and frequency of adverse events reported were generally similar to those seen in RA patients.

Section 5.1 – Pharmacodynamic properties: Under title ‘Immunogenicity’ information has been added regarding the drug tolerant enzyme immunoassay (EIA) method used in the pJIA phase III study for detection of antibodies to Golimumab. A higher incidence of antibodies was expected with this method and this was the case. However as they were manly low titre antibodies it did not have an impact on the drug levels, efficacy and safety and therefore does not represent a new safety signal.

The safety and efficacy evaluation of the GO-KIDS study has also been summarized.

Section 5.2 – Pharmacokinetic properties: Pharmacokinetics summary of golimumab evaluated in 173 children with pJIA has been added. Population PK/PD modeling and simulation in children with pJIA supports the dosage regimen.

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 19-Nov-2015

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Section 4.4 – Special warnings and precautions for use:
o Emphasize the risks of invasive fungal infections
o Clarify that cases of congestive heart failure (CHF) with fatal outcomes have been observed
o Clarify that leukemia has been observed in clinical trials in addition to the post marketing setting
Section 4.8 – Undesirable effects:
o Alignment of ‘Summary of the safety profile’ to the important identified risks in the RMP. Serious systemic hypersensitivity, vasculitis and leukaemia added.

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 22-Jun-2015

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Section 4.1 Therapeutic Indications: nr-Axial SpA has been added under the new title ‘Axial Spondyloarthritis’ along with AS.

Section 4.2 Posology and method of administration: nr-Axial SpA has been added to posology ‘Simponi 50 mg given once a month, on the same date each month’

Section 4.4 Special warnings and precautions for use: Under Elderly > 65 years within special populations it has been noted that the nr-Axial SpA study had no patients that were > 45 years old.

Section 4.8 Undesirable effects: nr-Axial SpA has been added as an indication throughout this section. “Description of selected adverse reactions” has been updated with regard to incidence numbers. The table in section 4.8 has been updated regarding the frequency of “Opportunistic infection” and “Bacterial arthritis”, both changing from Uncommon to Rare.

Section 5.1 Pharmacodynamic properties: A summary of the GO-AHEAD study has been added and a sentence under immunogenicity specifically referring to nr-axial SpA and antibodies to golimumab detected in 4% of treated patients through week 16.

Section 5.2 Pharmacokinetic properties: Reference to the steady state trough mean serum golimumab concentrations in patients with nr-Axial SpA being similar to patient with AS has been added to the Elimination paragraph.

Reasons for adding or updating:

• Change to section 6.3 - Shelf life
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 24-Apr-2015

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Section 6.3 – Shelf life: 1 year has been replaced with 18 months.

Reasons for adding or updating:

• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 15-Jan-2015

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Date of renewal added to Section 9 - 19th June 2014

Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text
• Correction of spelling/typing errors

Date of revision of text on the SPC: 25-Sep-2014

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        ·        Section 4.8 – Undesirable effects: bullous skin reaction has been added to the ADR table as an uncommon AE under SOC Skin and subcutaneous tissue disorders.
·        Section 5.1 – Pharmacodynamic Properties: A paragraph on antibody development has been re-instated after it was inadvertently removed from the SmPC during the UC procedure.

‘In the Phase II and III UC studies through week 54, antibodies to golimumab were detected in 3% (26/946) of golimumab treated patients. Sixty-eight percent (21/31) of antibody-positive patients had neutralizing antibodies in vitro. Treatment with concomitant immunomodulators (azathioprine, 6‑mercaptopurine and MTX) resulted in a lower proportion of patients with antibodies to golimumab than patients receiving golimumab without immunomodulators (1% (4/308) versus 3% (22/638), respectively).’

Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 26-Jun-2014

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Section 4.8 Undesirable effects

The frequency categories of a number of ADRs were amended based on the new clinical data, see below the affected ADRs:

Uncommon to Common	Lower respiratory tract infection (such as pneumonia), abscess; Depression, insomnia; paraesthesia; Asthma and related symptoms (such as wheezing and bronchial hyperactivity); gastrointestinal inflammatory disorders (such as gastritis and colitis), stomatitis; alopecia, dermatitis; chest discomfort; bone fractures
Rare to Uncommon	Pyelonephritis
Uncommon to Rare	Demyelinating disorders (central and peripheral), dysguesia; congestive heart failure (new onset or worsening); Raynaud’s phenomenon; , vasculitis (cutaneous); Bladder disorders, renal disorders;
Not known to Rare	Aplastic anaemia
Other changes	‘Septic shock, sepsis’ have been combined to read ‘Sepsis including septic shock’

 

In addition, the incidence rates (and their confidence intervals) in the description of selected ADRs were also updated based on the new clinical trial data.

 

Section 5.1 Pharmacodynamic properties

This section has been updated in order to reflect the safety and efficacy data (Week 104 through week 256) for studies:

·        RA Study C0524T05 GO-BEFORE

·        RA Study C0524T06 GO-FORWARD

·        RA Study C0524T011 GO-AFTER

·        Phase III Study in Psoriatic arthritis (C0524T08 - GO-REVEAL)

·        Phase III Study in Ankylosing Spondylitis (CO524T09 - GO-RAISE)

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 6.5 - Nature and contents of container
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 19-Jun-2014

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The changes made to the SmPC are as follows:

 

Section 4.2 Posology and method of administration

‘for all of the above indications’ now precedes the 2 paragraphs on clinical response under RA, PsA and AS.

 

Section 4.8 Undesirable effects

‘within each frequency grouping, adverse reactions are presented in order of decreasing seriousness’ has been added before the table of ADRs.

 

Section 5.1 Pharmacodynamic properties

‘HAQ’ has been replaced with ‘HAQ DI’

 

Section 6.5 Nature and content of container

1.0ml has been deleted from the description of type I glass: (1.0ml Type I glass)

 

Other changes have been applied throughout:

·        ‘ml’ now reads ‘mL’

·        ‘medications’ have been replaced with ‘medicines’

·        ‘Older people’ has been replace with ‘Elderly’

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 10 - Date of revision of the text
• Change to section 4.1 - Therapeutic indications

Date of revision of text on the SPC: 07-Oct-2013

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Wording added in section 4.1 Therapeutic Indication:

Ulcerative colitis (UC)

Simponi is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6‑mercaptopurine (6‑MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.

 

Wording added in section 4.2 Posology and method of administration:

Patients with bodyweight greater than 100 kg

In patients with RA, PsA or AS with a body weight of weighing more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses…………

 

Ulcerative colitis

Patients with body weight less than 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks, thereafter (see section 5.1).

 

Patients with body weight greater than or equal to 80 kg

Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter (see section 5.1).

 

During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.

 

Available data suggest that clinical response is usually achieved within 12‑14 weeks of treatment (after 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.

 

Method of administration paragraph includes the sentence: If multiple injections are required, the injections should be administered at different sites on the body.

 

Wording added in section 4.4 Special warnings and precautions for use:

 

Lymphoma and leukaemia

………..

Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with other TNF-blocking agents (see section 4.8). This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. The majority of cases have occurred in adolescent and young adult males with nearly all on concomitant treatment with azathioprine (AZA) or 6‑mercaptopurine (6–MP) for inflammatory bowel disease. The potential risk with the combination of AZA or 6‑MP and Simponi should be carefully considered. A risk for the development for hepatosplenic T‑cell lymphoma in patients treated with TNF-blockers cannot be excluded.

 

Malignancies other than lymphoma

In the controlled portions of the Simponi Phase IIb and Phase III clinical trials in RA, PsA, AS, and UC,

 

Colon dysplasia/carcinoma

It is not known if golimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated with Simponi, the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued.

 

Potential for Medication errors

Simponi is registered in 50 mg and 100 mg strengths for subcutaneous administration. It is important that the right strength is used to administer the correct dose as indicated in the posology (see section 4.2). Care should be taken to provide the right strength to ensure that patients are not underdosed or overdosed.

 

Wording added in section 4.8 Undesirable effects:

 

There have been many changes in the frequencies of ADRs:

Reduction in frequency	Increase in frequency
Common to uncommon Depression, insomnia, constipation, alopecia, dermatitis, chest discomfort	Rare to uncommon Pancytopenia, renal disorders
Common to rare Impaired healing
Uncommon to rare Tuberculosis, pyelonephritis, infective bursitis

Added:

‘Not known’ frequency – hepatosplenic T-cell lymphoma

 

Within the description of adverse drug reactions the UC trial data has been added making extensive changes to the number of golimumab treated patients, the number of control patients, the incidence per 100 subject years. Additional information has been added to the following ADRs:

Infections

In the controlled period of UC trials of golimumab induction, serious infections were observed in 0.8% of golimumab-treated patients compared with 1.5% of control-treated patients.

Malignancies

Malignancies other than lymphoma

Through approximately 2 years of follow-up, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar to the general population.

Liver enzyme elevations

In the controlled period of the UC pivotal trials of golimumab induction , mild ALT elevations (> 1 and < 3 x ULN) occurred in similar proportions of golimumab-treated and control patients (8.0% to 6.9%, respectively). In controlled and uncontrolled periods of the UC pivotal trials with a mean follow-up of 1 year, the incidence of mild ALT elevations was 17.4% in patients receiving golimumab during the maintenance portion of the UC study.

……..

In the controlled periods of the pivotal UC trials, of golimumab induction, ALT elevations ≥ 5 x ULN occurred in similar proportions of golimumab-treated patients compared to placebo-treated patients (0.3% to 1.0%, respectively). In the controlled and uncontrolled periods of the pivotal UC trials with a mean follow-up of 1 year, the incidence of ALT elevations ≥ 5 x ULN was 0.7% in patients receiving golimumab during the maintenance portion of the UC study.

 

Wording added in section 5.1 Pharmacodynamic properties:

‘Immunosuppressants’ has been added to the Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNF‑α) inhibitors, ATC code: L04AB06

 

Ulcerative colitis

The efficacy of Simponi was evaluated in two randomized, double-blind, placebo-controlled clinical studies in adult patients.

 

The induction study (PURSUIT-Induction) evaluated patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore ≥ 2) who had an inadequate response to or failed to tolerate conventional therapies, or were corticosteroid dependent. In the dose confirming portion of the study, 761 patients were randomized to receive either 400 mg Simponi SC at Week 0 and 200 mg at Week 2, 200 mg Simponi SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. Concomitant stable doses of oral aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted. The efficacy of Simponi through week 6 was assessed in this study.

 

The results of the maintenance study (PURSUIT-Maintenance) were based on evaluation of 456 patients who achieved clinical response from previous induction with Simponi. Patients were randomized to receive Simponi 50 mg, Simponi 100 mg or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of oral aminosalicylates, and/or immunomodulatory agents were permitted. Corticosteroids were to be tapered at the start of the maintenance study. The efficacy of Simponi through week 54 was assessed in this study.

 

Table 6

Key efficacy outcomes from PURSUIT - Induction and PURSUIT - Maintenance

PURSUIT-Induction
	Placebo N = 251	Simponi 200/100 mg N = 253
Percentage of patients
Patients in clinical response at week 6a	30%	51%**
Patients in clinical remission at week 6b	6%	18%**
Patients with mucosal healing at week 6c	29%	42%**
PURSUIT-Maintenance
	Placebod N = 154	Simponi 50 mg N = 151	Simponi 100 mg N = 151
Percentage of patients
Maintenance of response (Patients in clinical response through Week 54)e	31%	47%*	50%**
Sustained remission (Patients in clinical remission at both Week 30 and Week 54)f	16%	23%g	28%*
N = number of patients **    p ≤ 0.001 *      p ≤ 0.01 a      defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 or 1. b      Defined as a Mayo score ≤ 2 points, with no individual subscore > 1 c      Defined as 0 or 1 on the endoscopy subscore of the Mayo score. d      Simponi induction only. e      Patients were assessed for UC disease activity by partial Mayo score every 4 weeks (loss of response was confirmed by endoscopy). Therefore, a patient who maintained response was in a state of continuous clinical response at each evaluation through Week 54. f       A patient had to be in remission at both weeks 30 and 54 (without demonstrating a loss of response at any time point through Week 54) to achieve durable remission. g      In patients weighing less than 80 kg, a greater proportion of patients who received 50 mg maintenance therapy showed sustained clinical remission compared with those who received placebo .

 

More Simponi-treated patients demonstrated sustained mucosal healing (patients with mucosal healing at both Week 30 and Week 54) in the 50 mg group (42%, nominal p < 0.05) and 100 mg group (42%, p < 0.005) compared with patients in the placebo group (27%).

 

Among the 54% of patients (247/456) who were receiving concomitant corticosteroids at the start of PURSUIT-Maintenance, the proportion of patients who maintained clinical response through Week 54 and were not receiving concomitant corticosteroids at Week 54 was greater in the 50 mg group (38%, 30/78) and 100 mg group (30%, 25/82) compared with the placebo group (21%, 18/87). The proportion of patients who eliminated corticosteroids by Week 54 was greater in the 50 mg group (41%, 32/78) and 100 mg group (33%, 27/82) compared with the placebo group (22%, 19/87).

 

At Week 6, Simponi significantly improved quality of life as measured by change from baseline in a disease specific measure, IBDQ (inflammatory bowel disease questionnaire). Among patients who received Simponi maintenance treatment, the improvement in quality of life as measured by IBDQ was maintained through week 54.

 

Wording added in section 5.2 Pharmacokinetic properties:

Elimination

………..

Following induction doses of 200 mg and 100 mg golimumab at week 0 and 2, respectively, and maintenance doses of 50 mg or 100 mg golimumab subcutaneously every 4 weeks thereafter to patients with UC, serum golimumab concentrations reached steady state approximately 14 weeks after the start of therapy. Treatment with 50 mg or 100 mg golimumab subcutaneous every 4 weeks during maintenance resulted in a mean steady-state trough serum concentration of approximately 0.9 ± 0.5 mg/ml and 1.8 ± 1.1 mg/ml, respectively.

 

In UC patients treated with 50 mg or 100 mg golimumab subcutaneously every 4 weeks, concomitant use of immunomodulators did not have a substantial effect on steady-state trough levels of golimumab.

 

Linearity

………. Following a single SC dose in healthy subjects, approximately dose-proportional pharmacokinetics were also observed over a dose range of 50 mg to 400 mg.

 

Wording added in section 6.6 Special precautions for disposal and other handling:

Simponi should not be used if the solution is discoloured, cloudy or containing visible foreign particles. (this sentence has been deleted from section 6.5 and added to section 6.6)

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 25-Jul-2013

Legal Category:POM

Black Triangle (CHM): NO

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Section 4.2 and 4.3

‘Elderly patients’ has been replaced with ‘older people’.

 

Section 4.8:

‘Interstitial lung disease’ has been moved from Rare in the tabulated list of ADRs to Uncommon within SOC, thoracic and mediastinal disorders.

 

In line with the updated QRD template and Appendix V the following text will be added for 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 Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 27-Jun-2013

Legal Category:POM

Black Triangle (CHM): NO

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Wording added in section 4.4:

Vaccinations/therapeutic infectious agents

Patients treated with Simponi may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6). In patients receiving anti-TNF therapy, No limited data are available on the response to vaccination with live vaccines, risk of infection or on the secondary transmission of infection by with the administration of live vaccines to patients receiving Simponi. Use of live vaccines could result in clinical infections, including disseminated infections.

 

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with Simponi.

 

Wording added in section 4.5:

 

Live vaccines/therapeutic infectious agents

Live vaccines should not be given concurrently with Simponi (see sections 4.4 and 4.6).

Therapeutic infectious agents should not be given concurrently with Simponi (see section 4.4).

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 21-Mar-2013

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Black Triangle (CHM): NO

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Addition of text on TB risks/prophylaxis in section 4.4 :

“Cases of active tuberculosis have occurred in patients treated with Simponi during and after treatment for latent tuberculosis. Patients receiving Simponi should be monitored closely for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.”

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 19-Nov-2012

Legal Category:POM

Black Triangle (CHM): NO

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The changes made to the SmPC are as follows:

·        Warnings on concomitant use with other biologicals
Data based on a summary of published information from studies where anti-TNF treatment has been combined with another biological DMARD has resulted in updates to sections 4.4 and 4.5 of the SmPC in order to add a warning and updated information regarding concomitant use of golimumab/infliximab with other biological therapeutics.

 

 

·        MCC and melanoma safety warning
Following assessment melanoma is considered a drug class effect based on postmarketing data and the reporting rate associated with these data across TNF inhibitors, including infliximab and golimumab. The frequency category  is “rare” for of melanoma and "not known" for Merkel cell carcinoma, this has resulted in updates to sections 4.4 and 4.8 of the SmPC to add a warning and safety information regarding cases of melanoma and MCC. In addition, Section 4.4, subsection Malignancies, of the SmPC has been updated to advise that periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

 

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects
• Change to section 10 date of revision of the text
• Removal of Black Triangle

Date of revision of text on the SPC: 10-Sep-2012

Legal Category:POM

Black Triangle (CHM): NO

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The following changes to the SmPC were adopted:

•  Removal of the black triangle symbol.
• Addition of Rare side effect 'skin exfoliation' to section 4.8 Undesirable effects, under Skin and subcutaenous tissue disorders.

Reasons for adding or updating:

• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.3 - Contraindications
• Change to section 4.6 - Pregnancy and Lactation
• Change to section 4.8 - Undesirable Effects
• Change to section 5.2 - Pharmacokinetic Properties
• Change to section 9 - Date of first Authorisation/renewal of the Authorisation
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 06-Feb-2012

Legal Category:POM

Black Triangle (CHM): YES

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The changes to the product information (PI) include:

• Inclusion of Nausea to section 4.8 of the SmPC and section 4 of the PIL.
• Updates to the SmPC and PIL in line with QRD 8.0 for all other sections – PI Standard layout and terminology.

Reasons for adding or updating:

• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.4 - Special warnings and precautions for Use
• Correction of spelling/typing errors

Date of revision of text on the SPC: 05-Sep-2011

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Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Correction to replace the reference to 'Pre-Filled Syringe' in sections 2 and 4.4.
Minor correction to section 4.5 to remove reference to 'section 4.6' in the Concurrent use with anakinra and abatacept paragraph.

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 05-Sep-2011

Legal Category:POM

Black Triangle (CHM): YES

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Following a comprehensive review of clinical trial safety information for Simponi (golimumab) through approximately 3 years (Week 160), it was determined that the Simponi Core Reference Label required updating to provide the most recent clinical data and reflect the evolving safety profile of this product.

Scope
Section 4.8 of the SmPC is updated to include new clinical trial safety information for infections, malignancies, neurological events and liver enzyme elevations.

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.8 - Undesirable Effects
• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 27-May-2011

Legal Category:POM

Black Triangle (CHM): YES

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Indication extension: PsA structural damage
Scope: Extension of the indication to include psoriatic arthritis (PsA) structural damage. Section 4.1 has been updated to add the reduction in the rate of progression of peripheral joint damage in (PsA). Section 5.1 is updated regarding maintenance of the effects in signs and symptoms and physical function in PsA patients.
Background: wording has been added to the PsA indication to reflect data on structural joint damage measured by X-ray. Changes to section 5.1 are based on newly submitted X-ray data from the long-term extension of study C0524T08. This study was the basis for the initial approval of PsA.

Safety update related to leukemia and sarcoidosis
Scope: Update of section 4.8 of the SmPC regarding the frequency of leukaemia and inclusion of sarcoidosis, the latter in response to a CHMP request.
Background: The changes are in line with earlier recommendations from CHMP for sarcoidosis; however the frequency category is rare instead of unknown as one case has been reported from a clinical study. Since a case of T-cell type acute leukemia has been reported from a clinical study, the SmPC has been updated to change the frequency of leukemia from “not known” to “rare”, and remove the asterisk noting that leukemia has not been observed in clinical studies with golimumab.

Safety update related to neurological events
Scope: A paragraph has been added to section 4.8, stating that a greater incidence of demyelination (Neurological events) was observed in the golimumab 100 mg group compared with the golimumab 50 mg group. A cross-reference to section 4.8 has been added in the Neurological events paragraph in section 4.4.
Background: This change was proposed further to an additional review of demyelination events conducted to evaluate the occurrence of demyelinating disorders in the 100 mg group relative to 50 mg group.

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.6 - Pregnancy and Lactation
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 20-Apr-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



The Simponi SmPC has been updated to add information relating to transplacental transfer of golimumab to section 4.6  

Section 4.6: Pregnancy now reads:

There are no adequate data on the use of golimumab in pregnant women. Due to its inhibition of TNF, golimumab administered during pregnancy could affect normal immune responses in the newborn. Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The use of golimumab in pregnant women is not recommended; golimumab should be given to a pregnant woman only if clearly needed.

Golimumab crosses the placenta. Following treatment with a TNF-blocking monoclonal antibody during pregnancy, the antibody has been detected for up to 6 months in the serum of the infant born by the treated woman. Consequently, these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother’s last golimumab injection during pregnancy (see sections 4.4 and 4.5).

Section 4.4 and 4.6 of the SmPC have minor edits as a result of this change.

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects
• Change to section 7 - Marketing Authorisation Holder
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 22-Feb-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Section 4.8 of the SmPC has been updated to add vasculitis (systemic) as a rare side effect to immune system disorders and vasculitis (cutaneous) as an uncommon side effect to Skin and subcuteous tissue disorders.
These adverse drug reactions (ADR) were added to the SmPC following a request from the US Food and Drug Administration (FDA) to all manufacturers of TNFα blockers that vasculitis may be a potential safety issue associated with this class of drugs. The Marketing Authorisation Holder (MAH) reviewed the data on vasculitis to determine whether it should be added as an ADR for golimumab in the core reference labeling.

Also included in this revision is the change in the name of the MAH from Centocor B.V. to Janssen Biologics B.V.

 

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.8 - Undesirable Effects
• Change to section 5.2 - Pharmacokinetic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 27-Jan-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Update of section 4.1 of the SmPC (and related sections of the PL) to extend the indication in rheumatoid arthritis (RA) to include adult patients not previously treated with MTX; and addition of an indication for reduction in the rate of progression of joint damage in all RA populations. Related changes are made in section 5.1. In addition, changes have been introduced related to the SmPC guideline and implementation of the current QRD template.
Update of section 4.4 and 4.8 of the SmPC to add safety information regarding demyelinating disorders and update of section 4.4 regarding congestive heart failure.
Update of section 4.4 and 4.8 of the SmPC with additional safety information regarding serious hypersensitivity reactions.
Update of section 4.4 of the SmPC to add a recommendation for routine hepatitis B virus (HBV) testing as well as a recommendation to consult with a hepatitis B expert for patient tested positive for HBV infection.

Reasons for adding or updating:

• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 27-Oct-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Text has been added on the maintenance of treatment effect in patients with rheumatoid arthritis (RA), the revisions are based on data from the on going study in patients with inadequate response to DMARDS, data was provided up to week 104. For the 50 mg + MTX group it was determined that 54% (48/89) of subjects remained on the approved dose throughout the 2 years period. The ACR20/50/70 responses for these patients at week 104 have been added to section 5.1 of the SmPC, as well as information on maintenance of improvement in HAQ and SF-36 physical compontent.

The update of the information on immunogenicity data in section 5.1 was also supported appropriately by summarised data from all Phase 3 studies with golimumab in rheumatologic indications.

Reasons for adding or updating:

• New SPC for new product

Legal Category:POM

Black Triangle (CHM): YES