NICE Approval Research Articles

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

Spotlight commentary: Navigating between financial risks and improved treatment outcomes with immune checkpoint inhibitors in cancer patients: The need for biomarker identification and dose optimization.

Guideline for the treatment of chronic lymphocytic leukaemia

Guideline for the treatment of chronic lymphocytic leukaemia

P471 Real-world experience of using Tofacitinib in Ulcerative Colitis in biologic naïve and biologic exposed patients

Abstract Background Tofacitinib is an oral, small molecule, which recently received NICE approval for the treatment of moderate to severe treatment refractory ulcerative colitis (UC). We present data on the regional experience for it use in relation to its efficacy in a cohort of patients with UC. Methods This study analysed a retrospective, cohort from a large IBD unit in the UK. Patients with UC commenced on tofacitinib between 2019 and 2021 for active disease were included. Clinical disease activity was assessed at baseline, week 8, week 16 and during follow up visits. We evaluated clinical response (>50% reduction in symptoms) at week 8, proportion of patients requiring extended of induction therapy to week 16 and need for re-escalation of maintenance dosing. Results A total of 55 patients were included (median age 34 years; IQR 15.75). Twenty six (47.3%) patients had pancolitis, 20 (36.4%) were biologic naïve and 18 (32.7%) were exposed to more than one biologic. Eighteen patients (32.7%) entered clinical response at week 8 and were able to de-escalate to 5mg BD maintenance therapy. Six patients (10.9%) had a primary non response and required a switch to an alternative biologic or a colectomy. Of the patients given an extended induction period (10mg BD for 16 weeks), 7/31 (22.6%) were able to de-escalate to 5mg BD, 15/31 (48.4%) continued on 10mg BD as maintenance and 9/31 (29.0%) discontinued treatment due to lack of clinical response. Of the patients on 5mg BD as maintenance 10/24 (41.6%) required re-escalation to 10mg BD maintenance dosing following a median duration of 10 weeks. Primary non response to tofacitinib were similar in biologic naïve patients compared to biologic exposed patients (25% vs 28.5% respectively). Biologic exposed patients were more likely to need 10mg BD as maintenance dosing compared to biologic naïve patients (72% vs 46.7% respectively). Conclusion Consistent with prior literature, our experience confirms the effectiveness of Tofacitinib in both biologic naive and biologic exposed patients with moderate to severe UC with similar clinical response between the two cohorts. Patients exposed to biologics however appear to have a greater likelihood of escalation to 10mg BD for maintenance therapy.

The role of bempedoic acid in the management of dyslipidaemia

Bempedoic acid is a new oral lipid-lowering therapy which has been licenced for use in the United Kingdom. It can be used alone, with a statin, or with other lipid-lowering therapies where the target level for low density lipoprotein has not been achieved with these therapies alone. Bempedoic acid with ezetimibe can be prescribed for people who are unable to tolerate statins. This combination has received NICE approval following a technology appraisal. This paper discusses the place for of bempedoic acid as a lipid lowering drug and consider the mode of action, licensed indications, adverse drug reactions and the NICE technology appraisal recommendations.

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

NICE approval of selective internal radiation therapy for advanced HCC

NICE approval of selective internal radiation therapy for advanced HCC

Arts for the Blues: The development of a new evidence‐based creative group psychotherapy for depression

AbstractIntroductionDepression affects many adults in the UK, often resulting in referral to primary care mental health services (e.g. improving access to psychological therapies, IAPT). CBT is the main modality for depression within IAPT, with other approaches offered in a limited capacity. Arts psychotherapies are rarely provided despite their attractiveness to clients. However, the recent dropout rate of 64% within IAPT suggests that clients’ needs are not being fully met. Therefore, in order to expand clients’ choice we developed a new creative psychological therapy integrating evidence‐based approaches with arts psychotherapies.MethodA three‐level approach was used: (a) thematic synthesis of client‐identified helpful factors in evidence‐based approaches for depression and in arts psychotherapies; (b) studio practice exploring Cochrane Review findings on arts psychotherapies for depression; (c) pilot workshops for clients with depression and therapists.Findings and DiscussionEight key ingredients for positive therapy outcomes were identified: encouraging active engagement, learning skills, developing relationships, expressing emotions, processing at a deeper level, gaining understanding, experimenting with different ways of being and integrating useful material. These ingredients were brought together as Arts for the Blues for clients with depression: a 12‐session evidence‐based pluralistic group psychotherapy integrating creative methods as well as talking therapy.ConclusionThe evidence‐based foundation, creative content and pluralistic nature of this new approach aligned with eight client‐identified key ingredients for positive therapy outcomes make it a promising therapy option that can be adapted to individual therapy. Implications include consideration for NICE approval as an additional therapy for depression.

P87 CCG biologics pathways: re-introduction of the postcode lottery by stealth

Abstract Background NICE guidance approves pathways for inflammatory arthritis biologic therapies. Locally, CCG's commission pathways based on their interpretation of NICE guidance. For patients to have equal access to biologics, CCG pathways in different areas must be uniform. We examined whether CCG biologics pathways complied with this standard. Methods Using Freedom of Information requests, direct requests and internet searches, we found 21 approved biologics pathways in England for rheumatoid arthritis, 12 for psoriatic arthritis and 11 for ankylosing spondylitis. This covered 22.8 million people in England for RA (2017 population estimates). CCG Pathways were compared to NICE guidance with respect to restrictions and number of therapies allowed before an Individual Funding Request (IFR) was needed. Results We studied NICE guidance and determined an 'ideal' pathway for patients requiring > 1 biologic. All CCG pathways followed NICE guidance for 1st line biologics but there was significant variation for biologic failures. 18/21 CCG RA pathways indicated the maximum number of drugs that the CCG would commission without the clinician needing IFR. 7/18 allowed 1-3 biologics serially, 10/18 allowed 4-6 and 1/18 was unrestricted. Rituximab is NICE approved in RA in inadequate responders/intolerance to DMARDs/anti-TNF-α. 17/21 RA pathways allowed rituximab 1stline for haematological or treated solid malignancies, 4/21 did not. 6/21 CCG’s allowed rituximab 5 years after solid organ malignancy, 5/21 after 10 years, 10/21 did not specify or allow this usage. NICE guidelines for RA approve 11 biologics. 14/21 RA pathways allowed all 11 biologics, 7/21 pathways excluded sarilumab, tofacitinib or baricitinib or all three. NICE guidelines for PsA recommend the least expensive drug used first of the injected biologics or JAK inhibitors. IFR was required after 3 drugs in 9/12 pathways with 1/12 allowing 4 lines of therapy. For AS, 5/11 allowed 2 lines of therapy, the remainder 3 or 4 lines. Again, many pathways pre-specified which biologics could be used and excluded other NICE approved drugs at specific stages. Conclusion NICE specify the least expensive drug should be used for injected biologics with variation for administration mode/dosage. CCG’ s commission variably restrictive pathways potentially against NICE guidance, both with number and type of therapies before IFR submission is required. Some pathways allowed little scope to use therapies from earlier pathway points without breaching CCG limits. The IFR process for NICE approved therapies can exhibit wide variation in our experience with different outcomes for similar cases, and is time consuming with CCG decision making being opaque, despite NICE approval being legally enforceable. CCG biologic pathways introduce wide regional variation and potential unfairness in their interpretation of NICE guidance. This may disadvantage the worst affected patients who fail several therapies and prevent access to life changing therapy depending on geographical location. Disclosures J. Mistry None. D. Hill None. A. Kaul None.

P266 IL-4/13 inhibitor dupilumab associated with new onset peripheral axial spondyloarthritis in patients with atopic dermatitis

Abstract Background Dupilumab is a recombinant human monoclonal antibody that inhibits signalling of interleukin-4 and interleukin-13. It has NICE approval for use in patients with moderate to severe atopic eczema who have failed at least one standard therapy. The main reported side effects in clinical trials were allergic conjunctivitis (1-5%), injection site reactions (8-19%) and herpes viral infections (3-7%). Methods Here we report symptoms and signs of a new peripheral axial spondyloarthritis/ psoriatic arthritis type presentation in 8 patients within 16 weeks of commencing dupilumab. This has not been described previously in the clinical trials patient population. Results These patients had a long history of atopy with severe eczema and raised baseline IgE levels of > 12000. A positive response to dupilumab was seen in all patients as evidenced by marked improvements in the Eczema Area and Severity Index (EASI). Musculoskeletal symptom onset began between 2 and 16 weeks after commencement of drug. Patients typically complained of inflammatory type pain in the small joints and entheseal sites. 2/8 patients had inflammatory sounding spinal pain. Early morning stiffness was common. All patients had normal acute phase reactants and one patient had a positive rheumatoid factor. 6/8 patients had radiologically evident enthesitis as seen on MRI or ultrasound (power doppler ultrasound signal-PDUS). 3/8 patients had such severe symptoms that they had to discontinue dupilumab. All patients were commenced on non-steroidal anti inflammatories. One patient was commenced on a low dose JAK inhibitor and exhibited improvement in musculoskeletal symptoms. Conclusion IL-4 has been shown to suppress delayed type hypersensitivity reactions (DTHRs) in both human and mice studies. It has been demonstrated previously that IL-4 can prevent bone erosion and disease progression in animal models of inflammatory arthritis. Guenova et al (2015) showed that IL-4 can selectively suppress IL-23 transcription and secretion with reduced Th17 function. They suggest that administration of IL-4 may be of therapeutic benefit in Th17 mediated inflammatory conditions. Conversely, dupilumab through the inhibition of IL-4 and IL-13 and possible resultant increased IL-17 and IL-23 levels, has perhaps unmasked a tendency towards development of a peripheral axial SpA phenotype in these patients. Disclosures C.D. Hughes None. B. Menon None. Z. Willsmore None. R. Woolf None. C. Smith Grants/research support; CS is a PI/CoPI on a number of commercially supported studie (Abbvie, Janssen, Leo, Sanofi). A. Pink None. B.W. Kirkham Consultancies; BK has worked as a consultant for Eli Lilly, Gilead, Janssen and Novartis. Grants/research support; BK has received research support from Eli Lilly and Novartis.

O35 Efficacy & safety of tocilizumab in GCA: a multi-centre experience of NHS clinical practice

Abstract Background Giant cell arteritis (GCA) has a relapsing, remitting course with ischemic/vascular damage in a number of cases. Glucocorticoids (GC) remain mainstay of treatment with SAEs e.g. diabetes and fractures commonly seen. The GiACTA trial of tocilizumab (TCZ) in GCA led to NICE approval for 12 month’s therapy in relapsing/ refractory disease. We report real life experience in 51 cases. Methods Multicentre retrospective data collected through ENRAD and individual centres across England (Table 1). Outcomes were as assessed by supervising clinicians. Results Fifty-one patients were treated with TCZ (26 cranial, 13 LVV, 11 both). 11 (22.0%) had prior permanent sight loss due to AION, CRAO or both. One died prior to TCZ, from recurrent cerebral infarcts. Mean age was 71 years with 66.7% females. Ultrasound (US) was used for diagnosis in 28 (56.0%), exclusively or in combination with other tests such as biopsy, PET-CT or CTA. 70% had prior DMARD (LEF/MTX/AZT/MMF/CYC, mean duration 58 weeks). MTX was used in 50% alone or combination. Initial TCZ was given as subcutaneous or intravenous (85.4% and 14.6%). TCZ indication in 89.8% was relapsing, refractory or ischemic disease. Steroid AEs that prevented optimal GC dosing constituted 10% of TCZ indication. Mean follow up was 31 weeks, 30 (58.8%) continuing TCZ uninterrupted, 4 completed 12 months, 4 discontinued due to SAEs. Ten had brief interruptions due to minor AEs. One restarted after 12 months due to flare but died 12 weeks later from abdominal aortic aneurysm rupture. At follow up, 37(74%) were in remission with a mean GC dose of 6.97 mg (mean GC dose pre-TCZ 33.2 mg), Thirty-two (65.3%) ≤ 5mg. In 4 (8%) outcome could not be assessed as either they started TCZ recently or about to start. In 53% lipids were not checked after commencing TCZ. AEs seen were 37.0%. Conclusion In clinical practice, TCZ is efficacious and safe in relapsing/refractory/ischemic GCA. I.V. route is an option awaiting NHSE approval in refractory visual symptoms. Infections and other AEs do occur but overall safety profile is acceptable. US is excellent in identifying patients at need and is a useful disease activity monitoring tool. Disclosures A. Sebastian: None. A. Kayani: None. C. Ranasinghe: None. F. Hall: Consultancies; Sobi, S. Grants/research support; Actelion. C. Ransom: None. D. Jayne: None. V. Quick: Honoraria; Roche. M. Hughes: None. J. Stack: Member of speakers’ bureau; Roche. C. Mukhtyar: None. F. Coath: None. A. Bharadwaj: None. V. Hajela: None. S. Butler: Consultancies; Lily. M. Lwin: None. C. Edwards: Consultancies; Roche, Chugai. Grants/research support; Roche, Chugai. M. Whitlock: None. B. Dasgupta: Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.

No-chemo follicular lymphoma treatment gets NICE approval

No-chemo follicular lymphoma treatment gets NICE approval

From patent to patient: analysing access to innovative cancer drugs

Analysis of cancer drugs licensed through the European Medicines Agency (EMA) in 2000-2016 shows that the number of authorisations increased over that timeframe. The median number of licensed drugs each year rose from six for 2000-2008 to 13.5 for 2009-2016. Over 2000-2016, there were 64 drug authorisations for haematological, 15 for breast, and 12 for skin cancer, but none for oesophageal, brain, bladder, or uterine cancer. Only 6% of authorisations included a paediatric indication. The average time for a drug to progress from patent priority date to availability on the National Health Service (NHS) increased from 12.8 years for drugs first licensed in 2000-2008 to 14.0 years for those licensed in 2009-2016. There was evidence that the most innovative drugs were not being prioritised for EMA licensing and NICE approval.

WS03.08 Panel - Emerging Therapies - Immunotherapy

WS03.08 Panel - Emerging Therapies - Immunotherapy

The Impact of the Addition of Pertuzumab to Neoadjuvant HER2 Targeting on Pathological Complete Response (pCR) Rates: Kent Oncology Centre (KOC) Experience

Purpose: Neoadjuvant chemotherapy (NACT) with dual HER2 targeting improved pCR rates (ypT0ypN0) compared with herceptin plus chemotherapy in the TRYPHAENA and NeoSphere registration trials. Pertuzumab-containing regimens FEC-THP and TCHP were adopted at KOC following NICE approval (December 2016).

PB2094 A SINGLE CENTRE EXPERIENCE WITH AZACITIDINE FOR MDS, AML AND CMML IN RELATION TO CYTOGENETIC RISK AND PERFORMANCE STATUS

Background:Azacitidine is a hypomethylating agent which is used in the treatment of myelodysplastic syndromes (MDS), acute myeloid leukaemia (AML) and chronic myelomonocytic leukaemia (CMML). In the AZA‐001 trial, azacitidine altered the natural history of patients with higher‐risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival (OS) compared to conventional care regimens (24.5 months vs 15.0 months) and in particular improved OS in the poor risk cytogenetics group (17.4 months vs 6 months) which led to its NICE approval in 2011.Aims:We report a single centre experience over 4 years of using azacitidine in the licensed NICE indications and compared results to the published data.MethodsWe retrospectively reviewed patients with MDS, AML and CMML who received azacitidine at Ipswich Hospital NHS Trust between November 2014 and November 2018. Data was collected on demographics, disease characteristics, treatment, blood and platelet transfusion response, disease progression and cause of deathResults:Thirty‐nine patients met the NICE criteria for treatment and were included in the analysis, irrespective of the number of cycles received. Median age was 72.2 years. Male: Female ratio was 2:1. Median number of cycles was 9 (range from 1‐43). 51% of patients had a diagnosis of MDS, 31% AML and 18% CMML. 25.6% had poor risk cytogenetics as per the IPSS criteria. Median percentage of blasts on bone marrow aspirate was 15.7%. Causes of death were either disease progression or sepsis with only one death unrelated to the underlying condition (lung cancer). Median Kaplan‐Meier OS for all groups from the start of treatment with azacitidine was 18 months, with MDS patients OS of 22 months compared to 18 months for AML and 13 months for CMML (p = 0.22). There was a significant difference noted in the group who had poor risk (IPSS) cytogenetics versus other cytogenetic risks, with a median OS of 8 months and 20 months respectively (p = 0.002). A significant difference was also seen in the median OS based on performance status (PS), with an OS of 7 months, 20 months and not yet reached for PS 2, 1 and 0 respectively (p = 0.005).Summary/Conclusion:In the AZA‐001 trial median OS on azacitidine was 24 months vs. 18 months seen in our cohort. The AZA‐001 trial also showed improved OS for poor risk cytogenetics at 17.4 months vs. only 8 months seen in our experience. Although our data does support an overall improvement in median OS for all groups, our data showed less impressive results, with a 6 months less survival advantage in all groups and 9 months less OS in the poor cytogenetic group as compared to the trial data. As previously shown, we observed that the most significant factors in predicting OS were cytogenetic risks and PS. Interestingly, a large real world registry collection in Canada of 1101 patients on azacitidine over 6 years only showed a median OS of 12 months for all groups which further highlights the difference we often see between real world patients and trial data.

Pertuzumab gets NICE approval in advanced breast cancer

Pertuzumab gets NICE approval in advanced breast cancer

Post-operative, external, ultrasonic bone stimulation: preliminary experiences with mandibular healing

Introduction: External, high-frequency, ultrasonic bone stimulation (Exogen) has now developed a defined role in the management of tibial/fibular fracture non-unions. This gained NICE approval in 2013. Since then its therapeutic role in other axial fractures has been investigated. However, its role in OMFS remains unreported to date.

Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis.

To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales. Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend. We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates. Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.

Gliflozin monotherapy for type 2 diabetes: a review of NICE Technology Appraisal 390

Gliflozin monotherapy for type 2 diabetes: a review of <scp>NICE</scp> Technology Appraisal 390

PTU-062 Vedolizumab: Early Experience and Medium-Term Follow up Data from Two UK Tertiary IBD Centres

Introduction Vedolizumab was recently granted NICE approval for moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC). Novel pathways agreed by our CCG meant that patients at Guy’s & St. Thomas’ and King’s College Hospitals had early access to vedolizumab. Methods Records of patients commencing vedolizumab between Nov 2014–15 were screened. Those completing at least 14 weeks of treatment were included. Clinical activity was assessed using Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) at baseline, 14 and 30 weeks. Response: HBI/SCCAI reduction ≥3. Remission: HBI Results 60 patients (CD: 32, 53%, UC 25, 42%, IBD-U 3, 5%) commenced vedolizumab (m:f 29:31, age: 39 (18–74), follow-up: 5 months (1–13)). 19 were excluded from our analysis (3 IBD-U, 5 stomas, 11 treated for Of 32 patients with active disease at baseline, 17 (53%) responded and 11 (34%) achieved remission by week 14. The response and remission rates for CD were 8/15 (53%) and 6/15 (40%). In UC they were 9/17 (53%) and 5/17 (29%). Response and remission rates in anti-TNF experienced patients were 12/26 (46%) and 6/36 (35%) compared to 5/6 (83%) and 5/6 (83%) in anti-TNF naive patients, respectively. 7/11 (64%) with active disease at baseline who completed 30 weeks of treatment responded and achieved remission. Faecal calprotectin fell significantly (pre-induction: 1076 (90–4800), post-induction: 478 (10–3184), p = 0.029 for n = 14) and CRP remained stable (pre-induction: 4 (1–70), post-induction: 4 (1–72), p = 0.28 for n = 40). Rates of steroid use at each time point: 19/41 (46%) at baseline, 11/41 (21%) at week 14 and 3/15 (20%) at week 30. Surgery was required in 4/41 (10%, CD:3 and UC:1). Conclusion Our experience mirrors a previously reported real-world cohort 1 and demonstrates similar efficacy to the GEMINI trials. This data demonstrates a meaningful reduction in clinical and biochemical disease activity as well as a steroid-sparing effect in patients with complex and previously refractory disease. We did not see a significant difference in efficacy between patients with UC and CD. Reference 1 Christensen B. et al . Post-marketing experience of vedolizumab for IBD: The University of Chicago experience . ECCO; Barcelona, 2015. Disclosure of Interest None Declared