Ustekinumab

ArticlesRefrigerated StorageLactation Safety InformationNew Medicines ·
443644001

Articles

Refrigerated Storage

StelaraJanssen Cilag

Janssen Cilag
Stelara
45mg & 90mg pre-filled syringe, 45mg solution for injection, 130mg concentrate for solution for infusion.

In the event of an inadvertent temperature excursion the following data may be used:

Contact Janssen-Cilag Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

No Information
No Information
4 May 2020
London MI Service

Lactation Safety Information

For rheumatoid arthritis

For rheumatoid arthritis
See summary
Limited published evidence of safety indicates negligible to small amounts in breast milk which are likely to be degraded in the infant’s GI tract
Very long half-life increases risk of accumulation in breastfed infants
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
22 January 2020

For psoriasis

For psoriasis
Topical psoriasis preparation / corticosteroid if appropriate
Limited published evidence of safety indicates negligible to small amounts in breast milk which are likely to be degraded in the infant’s GI tract
Very long half-life increases risk of accumulation in breastfed infants
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
22 January 2020

For inflammatory bowel disease

For inflammatory bowel disease
See summary
Limited published evidence of safety indicates negligible to small amounts in breast milk which are likely to be degraded in the infant’s GI tract
Very long half-life increases risk of accumulation in breastfed infants
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
22 January 2020

New Medicines

StelaraModerate-to-severe active ulcerative colitis in adults

Information

Stelara
Licence extension / variation
Janssen
Johnson & Johnson

Development and Regulatory status

Launched
Launched
Launched
September 2019
Oct 19Approved in US [11].
Oct 19PIII pivotal UNIFI trial demonstrated >40% of patients receiving ustekinumab SC injections every 8 weeks were in clinical remission at one year and not taking corticosteroids [9].
Sep 19Licence change approved in EU [8].
Jul 19Recommended for EU approval by CHMP - the additional indication is "for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic or have medical contraindications to such therapies (see section 5.1)." [7].
Jan 19Application has been made to EMA seeking approval of STELARA® (ustekinumab) for the treatment of adults with moderately to severely active ulcerative colitis (UC)[5].
Dec 18Supplemental Biologics License Application (sBLA) submitted to the FDA seeking approval of ustekinumab) for the treatment of adults with moderately to severely active ulcerative colitis[4].

Category

Human monoclonal antibody that targets the p40 subunit of interleukin-12 (IL-12) AND interleukin-23 (IL-23), preventing them from binding to their receptors on T-cells and natural– killer cells.
Ulcerative colitis is the most common type of inflammatory disease of the bowel. It has an incidence in the UK of approximately 10 per 100,000 people annually and a prevalence of approximately 240 per 100,000. Ulcerative colitis can develop at any age but peak incidence is between the ages of 15 and 25 years, with a second, smaller peak between 55 and 65 years [2].
Moderate-to-severe active ulcerative colitis in adults
Intravenous infusion and
Subcutaneous injection

Further information

Yes
To be confirmed

Trial or other data

Oct 19Two-year data from the long-term extension of the PIII UNIFI study (n=399) demonstrated majority of patients who achieved symptomatic remission with ustekinumab were able to sustain remission through week 92 (69% on 8-weekly and 80% on 12 weekly regimen) [10].
Mar 19Further positive results from PIII UNIFI study ustekinumab as maintenance therapy in adults with moderate to severe UC announced at conference. More patients on ustekinumab achieved complete remission at week 52 vs placebo (44% of adults receiving ustekinumab every 8 weeks and 38% receiving ustekinumab every 12 weeks vs 24% of patients on placebo (both p<0.001) [6].
Oct 18Positive 8-week induction data announced from PIII UNIFI study in pts with severe Ulcerative Colitis (UC). At wk 8, 15.6% of pts receiving ustekinumab 130 mg and 15.5% of pts receiving ~6 mg/kg ustekinumab achieved clinical remission vs. 5.3% of pts receiving placebo (p11. Endoscopic healing (endoscopy subscore of 0 or 1) occured in 26.3% and 27.0% receiving ustekinumab 130mg and 6 mg/kg respcteivly vs. 13.8% receiving placebo (p<0.001). Clinical response (decrease of ≥30% in Mayo score and ≥3 points + decrease in rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 11) occurred in 51.3% and 61.8% of pts receiving ustekinumab 130mg and 6mg/kg respectively vs. achieved 31.3% receiving placebo (p<0.001). Similar improvements were seen in mucosal healing and symptom scores (secondary endpoints). Adverse were of similar proportions across ustekinumab and placebo gps. No malignancies, opportunistic infections or tuberculosis infections were reported through Week 8. One death from oesophageal varices haemorrhage was reported for a pt with no known history of cirrhosis or portal hypertension in the ~6 mg/kg dose group prior to wk 8.[3]
Oct 16PIII UNIFI is still recruiting pts [1].
Jul 15PIII UNIFI study (NCT02407236) to evaluate the efficacy and safety of ustekinumab as intravenous infusion in an induction study in participants with moderately to severely active Ulcerative Colitis (UC) and as subcutaneous (SC) administration in a maintenance study in participants with moderately to severely active UC who have demonstrated a clinical response to Induction treatment with IV ustekinumab. [1]. 951 adults will be recruited from sites globally, inlcuidng US & EU (plus UK). Primary outcome in the Induction Study is number of participants With clinical remission at week 8 (The global definition of Clinical remission is defined as Mayo score less than or equal to () 1, for countries outside the United States (US). For the US, Clinical remission is defined as absolute stool number <=3, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, findings on flexible sigmoidoscopy and physician´s global assessment), each subscore is graded from 0 to 3 with the higher score indicating more severe disease activity). In the Maintenance Study primary outcome is number of participants with clinical remission among participants in clinical response to IV Ustekinumab Induction Treatment at week 44. Collection of these data should complete Apr 18 [1].

Evidence based evaluations

StelaraPsoriasis in children (6-11 years)

Information

Stelara
Licence extension / variation
Janssen
Johnson & Johnson

Development and Regulatory status

Launched
Launched
Launched
January 2020
Jul 20Approved in US [11].
Jan 20The EC has approved the expanded use of STELARA® (ustekinumab) for the treatment of paediatric patients (ages 6–11) with moderate to severe plaque psoriasis [10].
Dec 19Recommended for EU approval by CHMP - the amended paediatric plaque psoriasis indication is the treatment of moderate to severe plaque psoriasis in children and adolescent patients from the age of 6 years and older, who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies (previously only licensed for use in children from the age of 12 years) [9].
Oct 19A supplemental Biologics License Application (sBLA) has been made to the FDA seeking expanded approval of ustekinumab to treat pediatric (ages 6-11) patients with moderate to severe plaque psoriasis [7].
Jun 19Filed in EU [8].
Nov 18PIII in EU & US for paediatric psoriasis; estimated primary completion date for NCT02698475 is Nov 2018 [5,6].
Oct 17PIII in EU & US for paediatric psoriasis [4].

Category

Interleukin 12/23 inhibitor
Although pediatric psoriasis is not uncommon, limited epidemiology data are available to date. It is estimated that approximately 30–50 % of adults with psoriasis developed psoriasis before 20 years of age. Prevalence of psoriasis in childhood in the UK is about 0.55 % in children aged 0–9 years and 1.37 % in children aged 10–19 years [1].
Psoriasis in children (6-11 years)
Subcutaneous

Trial or other data

Nov 17PIII (NCT02698475) study has completed recruitment, and expects to complete collection of primary outcome data (Physician´s Global Assessment of Cleared [0] or Minimal [1] at Week 12) in Sep 18 [3].
May 16PIII CADMUS Jr trial to assess the pharmacokinetics, efficacy and safety of ustekinumab SC (0.75 mg/kg, 45mg and 90mg) in paediatric patients (aged 6 to 11 years) with moderate to severe chronic plaque psoriasis starts (NCT02698475). The single-group, open-label trial will enrol approximately 40 patients in Belgium, Germany, Hungary, South Korea and Taiwan [2].

Evidence based evaluations

StelaraActive systemic lupus erythematosus (SLE) - second-line

Information

Stelara
Licence extension / variation
Janssen
Johnson & Johnson

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Jun 20Janssen decides to terminate this clinical program based the outcome from a pre-planned interim analysis for efficacy which has shown a lack of differentiation between ustekinumab and placebo. There were no new safety signals identified in the interim analysis, and the observed safety profile was consistent with the known safety profile of ustekinumab. As the decision to terminate the study was made solely due to lack of efficacy in SLE, the outcome of this study does not impact the approved indications or other ongoing studies [7].
Jun 20PIII trial suspended due to lack of efficacy. The company intends to thoroughly analyze the totality of the study data and publish findings [6].

Category

A fully human interleukin (IL)-12 and IL-23 antagonist
Lupus is estimated to affect at least 1.5 million Americans and 5 million people worldwide. The disease most often affects women and disproportionately affects women of African American, Hispanic, Asian and Native American descent compared to Caucasian women [1]
Active systemic lupus erythematosus (SLE) - second-line
Intravenous &
Subcutaneous

Ustekinumab biosimilar (FYB202)Psoriasis

Information

Ustekinumab biosimilar (FYB202)
Biosimilar
Formycon
Formycon

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Human monoclonal antibody that targets cytokines interleukin-12 and interleukin-23.
The prevalence of psoriasis is estimated to be about 1.3-2.2% in the UK [2].
Psoriasis
Subcutaneous injection

Ustekinumab biosimilar (ABP654)Psoriasis

Information

Ustekinumab biosimilar (ABP654)
Biosimilar
Amgen
Amgen

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

A biosimilar of monoclonal antibody ustekinumab, that binds to the p40 subunit of interleukin-12 and IL-23, and inhibits their activities, thereby preventing these cytokines from binding to their receptors expressed on natural killer T-cells.
The prevalence of psoriasis is estimated to be about 1.3-2.2% in the UK, with the highest prevalence being in white people. Men and women are equally affected. It can occur at any age but the majority of cases first present before the age of 35 years. It is uncommon in children [1].
Psoriasis
Subcutaneous injection

Psoriasis, Crohn's disease, ulcerative colitis

Information

Biosimilar
Celltrion
Celltrion

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Human monoclonal antibody that targets the p40 subunit of interleukin-12 (IL-12) AND interleukin-23 (IL-23), preventing binding to T-cells and natural–killer cells. Given initially as 2 doses 4 weeks apart, then 12-weekly.
The prevalence of psoriasis is estimated to be about 1.3-2.2% in the UK, with the highest prevalence being in white people [2].
Psoriasis, Crohn's disease, ulcerative colitis
Subcutaneous injection