2015/16 PBR Exclusions – Funding Application for Infliximab, Adalimumab, GolimumabandVedolizumab for treating Moderately to Severely Active Ulcerative Colitis(Final version 1: Last updated 16/07/2015)
Before providing patient identifiable data on this form, please confirm that the patient (or in the case of a minor or vulnerable adult with the parent/legal guardian/carer) has given appropriate explicit consent for sensitive personal information on this form to be passed to the CCG and/or CSU for processing this funding request and validating subsequent invoices. Consent given: YesIf there is more than one NICE-approved treatment available, a discussion between the responsible clinician and the patient has taken place about the advantages and disadvantages of the treatments available. This has taken into consideration therapeutic need and whether or not the patient is likely to adhere to treatment. The least expensive will be chosen (taking into account administration costs, dosage and price per dose) unless an order of preference is stated in the TAs. Yes
Patient NHS Number: / Trust: / GP Name:
Patient Hospital Number: / GP /Practice code:
Patient Birth Year: / (yyyy) / Requesting Consultant:
Patient Status:(* select 1 option) / NHS / Private / Overseas / Consultant Contact Details: / Practice Postcode:
Please indicate whether the patient meets ALL of the following criteria / Please tick / Only fully completed forms will be accepted by CCGs/CSUs for consideration.
If the answer to any of these questions is NO, please consider if there are patient specific exceptional clinical circumstances demonstrated. If so, a full individual funding request (IFR) form will need to be completed. This may be obtained from the named contact at the relevant CCG/CSU/Trust. Please refer to the individual CCG IFR policy for further details.
Contact details:
Form completed by:
Email (NHS net):
Phone:
Date of completion:
Additional Information:
Is the patient aged 18 years or over? / Yes / No
Patient has moderately or severely active Ulcerative Colitis that would normally be managed in an outpatient setting and does not require hospitalisation or the consideration of urgent surgical intervention.
*For acute exacerbations of acute severely active ulcerative colitis use ‘Funding application for Infliximab for acute exacerbations of Ulcerative Colitis’ (NICE TA 163)* / Yes / No
Patient had responded inadequately to conventional therapy before starting any biologic drug including corticosteroids and mercaptopurine or azathioprine, or cannot tolerate, or has medical contraindications for such therapies. / Yes / No
Which treatments have been tried in this patient before any biologic (tick which applies) / Dose / Start date / Stop date / Please indicate that the patient has either not responded/ is intolerant/ has a contraindication to or is continuing on treatments (provide details including type of intolerance)
5-ASA (specify: )
Corticosteroids
Azathioprine**
6-Mercaptopurine**
Other non-biologic treatment (please specify)
Other non-biologic treatment (please specify)
** Azathioprine/6-Mercaptopurine should be given at maximum tolerated doses for a minimum of 3 months following dose titration.
Consider switch to 6-Mercaptopurine in case of adverse drug reactions with Azathioprine before starting biologic. In case of deranged liver function consider adding Allopurinol to reduced dose thiopurine before starting biologic.
Biologic history (where applicable) / Start date / Stop date / Reason for stopping (including remissions)
Adalimumab
Golimumab
Infliximab
Vedolizumab
One of the following options applies (select one option):
Patient is biologic naïve (go to 6)
CCG approved 1st line biologic treatment had to be stopped due to an adverse event before efficacy could be assessed. (Adalimumab 8 weeks, Golimumab/Infliximab 14 weeks, Vedolizumab 10 weeks). Provide brief details on adverse event: (go to 6)
Patient was responding to CCG approved 1st line biologic treatment but this had to be stopped due to an adverse event after 8 weeks (Adalimumab), 14 weeks (Golimumab/Infliximab) or 10 weeks (Vedolizumab)of initiation. Provide details on adverse event: (go to 5)
Patient had responded to treatment with 3 doses of Infliximab after an acute exacerbation of ulcerative colitis (initiated under NICE TA 163) in the past and despite subsequent optimisation of conventional (non-biologic) therapy has moderate to severe ulcerative colitis (go to6)
Patient has responded to a CCG approved 1st line biologic treatment (for moderately to severely active ulcerative colitis) in the past and requires retreatment for a moderate or severely active Ulcerative Colitis episode that has not responded adequately to dose optimisation of conventional (non-biologic) therapy (go to6)
Request is for Vedolizumab - Patient had an inadequate response or has lost response to CCG approved 1st line biologic. Please provide brief details: Start date: Stop date: (go to 6)
Sequential treatment with anti-TNF inhibitors (Adalimumab, Golimumab, Infliximab) due to primary or secondary failure of a biologic is not routinely commissioned. / Yes / No
There is evidence of response to biologic treatment and all of the following applies (provide details belowthen go to 7)
There was a decrease in full Mayo score from baseline of at least 3 points and at least 30% OR partial Mayo score of at least 2 points and 25%
There was a decrease in the rectal bleeding sub-score from baseline of at least 1 point OR the absolute rectal bleeding sub-score was 0 or 1
Patient was NOT yet in clinical remission (e.g. Mayo score > 2 with individual sub-scores > 1). / Yes / No
Measurement
[see page 8 for details of Mayo score] / Prior to biologic treatment / When stopping biologic due to adverse event / Change
Full Mayo score OR
Partial Mayo score* (select one) / Total:Date: / Total: Date: / points %
Stool frequency
Rectal bleeding / points
Endoscopic findings (N/A for partial Mayo)
Physician global assessment
*If partial Mayo score is used, provide Faecal Calprotectin level (if available) / mcg/g Date: / mcg/g Date:
One of these applies after failure of optimised conventional therapy and prior to starting requestedcourse of biologic treatment [see page 8 for details of Mayo score](tick one and provide details):
Full Mayo score 6. Score:Date:OR
Partial Mayo score 4. Score:Date:AND Faecal Calprotectin >100mcg/g:mcg/g Date:
(if available) / Yes / No
Stool frequency / Endoscopic findings (N/A for partial Mayo)
Rectal bleeding / Physician global assessment
Please specify which drug is requested:
Adalimumab (go to 10) Golimumab(go to 8) Vedolizumab (go to 9)
Remsima® (infliximab biosimilar)* (go to 10) Inflectra® (infliximab biosimilar)* (go to 10) Remicade® (infliximab)* (go to 10)
*Remsima® is the preferred Infliximab brand for all London Trusts.
Please provide valid reason, if not using preferred biosimilar:
Note: In London Adalimumab (standard dose) is the least expensive followed by Golimumab, Infliximab biosimilar (taking into account
cost of administration for the latter), Infliximab (Remicade®) and Vedolizumab. Vedolizumab is the most expensive biologic and should
therefore not normally be considered as first line treatment.
Sequential treatment with anti-TNF inhibitors (Adalimumab, Golimumab, Infliximab) due to primary or secondary failure of a biologic is not routinely commissioned.
For Golimumab, the manufacturer will provide the 100mg dose at the same cost as the 50mg dose (go to 10) / Yes / No
For Vedolizumab, the manufacturer will provide the drug at the discount agreed in the patient access scheme. / Yes / No
Licensed induction and standard* maintenance dose / frequency of requested biologic drug will be used?
(*Vedolizumab 8 weekly) Drug dose and frequency: For Infliximab: Patient weight kg / Yes / No
What is acquisition cost per month/dose at maintenance dose (including VAT if applicable)
Note: CCGs will not pay more than the London Procurement list price/PAS price. Commercial in confidence for Trust/CCG/CSU / £ / dose (Infliximab/Vedolizumab)
£ / month (Adalimumab/Golimumab)
FOR CCG/CSU USE ONLY / Monitoring and Stopping Criteria
Funding is approved for a planned course of treatment (for an induction period followed by maintenance treatment) until treatment failure (including the need for surgery) or until 12 months after the start of treatment (whichever is shorter) / Yes / No / Trial withdrawal: Following the 12 months planned course, treatment should only be continued if there is clear evidence of response as determined by clinical symptoms, biological markers and investigation, including endoscopy if necessary. According to NICE TA, a trial withdrawal from treatment should be considered for all patients who are in stable clinical remission. (See 4.4 – A Mayo score of 2 or less with no individual sub-score greater than 1 is considered to be remission)
If continued treatment is appropriate: If a patient is to continue with treatment beyond 12 months (rather than a trial withdrawal), the clinician is required to write to the CCG/CSU with a clinical update providing details that the patient has had a response to treatment but that they are not in stable clinical remission. The following should be provided at this point as per NICE TA (section 4.4)
- Decrease in full Mayo score from baseline of at least 3 points and at least 30 % or partial Mayo score of at least 2 points and 25%.
- A decrease in the rectal bleeding sub-score from baseline of at least 1 point, or having an absolute rectal bleeding sub-score of 0 or 1.
Funding is re-approved (12 monthly intervals) / Yes / No
Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of NICE TA 140 and TA 262) (NICE TA 329: February 2015)
1.1Infliximab, adalimumab and golimumab are recommended, within their marketing authorisations, as options for treating moderately to severely active ulcerative colitis in adults whose disease has responded inadequately to conventional therapy including corticosteroids and mercaptopurine or azathioprine, or who cannot tolerate, or have medical contraindications for, such therapies.
Golimumab is recommended only if the company provides the 100 mg dose of golimumab at the same cost as the 50 mg dose, as agreed in the patient access scheme.
1.2The choice of treatment between infliximab, adalimumab or golimumab should be made on an individual basis after discussion between the responsible clinician and the patient about the advantages and disadvantages of the treatments available. This should take into consideration therapeutic need and whether or not the patient is likely to adhere to treatment. If more than 1 treatment is suitable, the least expensive should be chosen (taking into account administration costs, dosage and price per dose).
1.4 Infliximab, adalimumab or golimumab should be given as a planned course of treatment until treatment fails (including the need for surgery) or until 12 months after starting treatment, whichever is shorter. Specialists should then discuss the risks and benefits of continued treatment with the patient, and their parent or carer if appropriate:
- They should continue treatment only if there is clear evidence of response as determined by clinical symptoms, biological markers and investigation, including endoscopy if necessary. People who continue treatment should be reassessed at least every 12 months to determine whether ongoing treatment is still clinically appropriate.
- They should consider a trial withdrawal from treatment for all patients who are in stable clinical remission. People whose disease relapses after treatment is stopped should have the option to start treatment again.
4.2All the RCTs except the study by Probert et al. used the Mayo score to assess the eligibility of patients. The Mayo score assesses 4 outcomes (stool frequency, rectal bleeding, endoscopic findings and physician's global assessment) on a scale of 0–12, with the score increasing with disease severity. In all these trials patients were eligible if they had a Mayo score of 6–12 with disease identified by endoscopic examination, which represents moderate to severe disease. Probert et al. used instead the ulcerative colitis symptom score, but the Assessment Group considered this to be equivalent to the Mayo score. Patients had to have taken conventional therapies before. These therapies varied across the trials but generally included corticosteroids, aminosalicylates and/or a drug that affects the immune response. Only in ULTRA2 were patients allowed to have had a TNF‑alpha inhibitor before (40% of patients had been treated with one). Patients were excluded from the trials if they had any of the following: ulcerative proctitis (ulcerative colitis that is limited to the rectum), a history of or a risk of having bowel surgery, diseases of the central nervous system, previous serious infection or a deficient immune system, previous cancer, or dysplasia (signs of abnormal growth of cells).
4.4The primary end point in all the RCTs was clinical response or remission. Of the 9 trials in adults, 8 trials assessed how well the treatment induced clinicalresponse or remission, and 6 trials assessed how well the treatment maintained it (5 trials assessed both). To assess clinical response or remission, all trials except the study by Probert et al. used the Mayo score, which the Assessment Group considered to be applied consistently in the individual trials. Probert et al. used the ulcerative colitis symptom score. In the trials that used the Mayo score, clinical response was generally defined as:
- a decrease in Mayo score from baseline of at least 3 points and at least 30%, and
- a decrease in the rectal bleeding sub‑score from baseline of at least 1 point, or having an absolute rectal bleeding sub‑score of 0 or 1.
Vedolizumab for treating moderately to severely active ulcerative colitis (NICE TA 342: June 2015)
1.1 Vedolizumab is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults only if the company provides vedolizumab with the discount agreed in the patient access scheme.
1.2 Vedolizumab should be given until it stops working or surgery is needed. At 12 months after the start of treatment, people should be reassessed to see whether treatment should continue. Treatment should only continue if there is clear evidence of ongoing clinical benefit. For people in complete remission at 12 months, consider stopping vedolizumab, resuming treatment if there is a relapse. People who continue vedolizumab should be reassessed at least every 12 months to see whether continued treatment is justified.
2.1 … The marketing authorisation states that vedolizumab is indicated 'for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, or lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha antagonist'. The recommended dosage of vedolizumab is 300 mg given by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter. Continued therapy for people with ulcerative colitis should be carefully reconsidered if no evidence of therapeutic benefit is observed by week 10.
3.1 …Clinical response was measured using the Mayo score, which included assessment of stool frequency, rectal bleeding, an endoscopic assessment and a global assessment by a clinician. Clinical response was defined as a reduction in the Mayo score of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an overall rectal bleeding subscore of 1 point or less. Secondary outcomes included clinical remission (Mayo score of up to 2 points and no individual subscore greater than 1 point) and mucosal healing (defined as an endoscopic subscore of 1 point or less).
3.2 GEMINI I included people who had moderate to severely active ulcerative colitis at baseline (Mayo score of 6 to 12).
3.6 … Clinical response was assessed by the partial Mayo score (that is, the Mayo score without the sigmoidoscopy subscore). Response was defined as a reduction of at least 2 points and a decrease of at least 25% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of up to 1 point.
Costing statement: Ulcerative colitis – Implementing the NICE guidance on infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (TA329)
cMaintenance doses of adalimumab (40 mg) may in some cases be used each week, as opposed to every 2 weeks (the standard regimen). Based on a response to the consultation it has been assumed that 15.9% of people receiving adalimumab are treated every week. Costs vary depending the dose prescribed, and.the above costs for adalimumab have been weighted to reflect this.
Costing statement: Ulcerative colitis – Implementing the NICE guidance on vedolizumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (TA342)
a Induction doses at 0,2 and 6 weeks. Maintenance doses every 8 weeks thereafter.
NICE enq ref EH56265 RE: NICE technology appraisal guidance [TA329]– email correspondence 06th May 2015
I can advise you that the guidance does not cover the sequential use of treatments as this was outside the scope of the appraisal. This means that it is the responsibility of local commissioners to make their own decisions regarding funding of TNF-alpha inhibitors after previous failure or adverse events. We have reviewed the SPCs and they do not make any mention on the use of the drugs in people who have previously received a different TNF-alpha inhibitor, although they are not contraindicated in these people.