Pharmacoeconomic evaluation of Secukinumab use as a first- line biologic in patients with psoriatic arthritis

2018 ◽  
Vol 6 (4) ◽  
pp. 20-28
Author(s):  
R.I. Yagudina ◽  
A.Yu. Kulikov ◽  
V.G. Serpik ◽  
P.A. Logvinyuk ◽  
M.V. Protsenko ◽  
...  
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1672.2-1672
Author(s):  
N. Busquets-Pérez ◽  
C. Sánchez-Piedra ◽  
P. Vela-Casasempere ◽  
M. Freire-Gonzalez ◽  
C. Bohórquez ◽  
...  

Background:Ustekinumab has been efficacy and safety for psoriatic artritis in clinical trials.Objectives:To assess effectiveness, by means of drug persistence analisys, and safety of ustekinumab in patients with psoriastic arthritis in Biobadaser.Methods:BIOBADASER is the Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency. We identified patients aged 18 years or more with psoriatic arthritis on Ustekinumab. A descriptive analysis was performed.The persistence of ustekinumab therapy was calculated with a Kaplan-Meier curve and was compared with the persistence of anti-TNF, according to line treatment. Log Rank test was used to establish a comparison. Adverse events occurring with ustekinumab are described according to year treatment.Results:One hundred and twelve patients were on ustekinumab. Most of them were on their second or third line treatment: 53.57% more than one biological therapy (BT), 19.64% second BT, 26.79% were naïve for BT. Most of them were on 45 mg dose: 88.24%. Median duration of disease at Ustekinumab initiation was 10.1 SD 7.2 years; 69.23% had peripheral arthritis; 45.24% had obesity and 39.29% were overweight; 40,6% were on prednisone and 59.82% on DMARD. The cause of discontinuation of treatment was mainly inefficacy (82.61%) and less common an adverse event (6.52%). The probability of persistence of treatment with ustekinumab was 0.83 (95% CI 0.63-0.92) at year 1, 0.79 (0.58-0.90) at year 2 and 0.79 (0.58-0.9) at year 3 when ustekinumab was prescribed as the first line treatment. The persistence decrease when ustekinumab was prescribe as a second and third treatment: being 0.53 (0.27-0.73) the first year, 0.46 (0.22-0.67) the second year and 0.46 (0.22-0.67) as a second line treatment and 0.58 (0.44-0.70) the first year, 0.33 (0.17-0.50) the second year and 0.33 (0.17-0.50) the third year as a third line treatment.The persistence was similar to anti-TNF treatment, according to line treatment. Adverse events were mainly mild (97.83%) and occurred the first year of treatment. Most of the adverse events were classified as “infections and infestations” (36.96%).Conclusion:The persistence of ustekinumab was high, being 83% at the end of the first year on treatment and 79% the second and the third year of treatment. The persistence of ustekinumab was higher when if it was the first line treatment compared as if it was used as the second o third BT option. The persistence of Ustekinumab is similar to the persistence of anti-TNF treatments in all the analyzed treatment lines (no statistically differences were found). Adverse events occurred mainly during the first year treatment. They were mainly mild adverse events and the frequency decreased within the second and third year of treatment.References:[1]Treatment with ustekinumab in a Spanish cohort of patients with psoriasis and psoriatic arthritis in daily clinical practice.Almirall M, Rodriguez J, Mateo L, Carrascosa JM, Notario J, Gallardo F. Clin Rheumatol. 2017 Feb;36(2):439-443;[2]Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study.Napolitano M, Costa L, Caso F, Megna M, Scarpa R, Balato N, Ayala F, Balato A. J Clin Rheumatol. 2018 Oct;24(7):381-384;[3]Minimal Disease Activity and Patient-Acceptable Symptom State in Psoriatic Arthritis: A Real-World Evidence Study With Ustekinumab.Queiro R, Brandy A, Rosado MC, Lorenzo A, Coto P, Carriles C, Alperi M, Ballina J. Actas Dermosifiliogr. 2018 Jun 28;[4]An analysis of Drug Survival, Effectiveness, and Safety in Moderate to Severe Psoriasis Treated With Ustekinumab: An Observational Study of 69 Patients in Routine Clinical Practice.Salgüero Fernández I, Gil MH, Sanz MS, Gullón GR;Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 58.2-59
Author(s):  
O. Palsson ◽  
T. Love ◽  
J. K. Wallman ◽  
M. C. Kapetanovic ◽  
P. S. Gunnarsson ◽  
...  

Background:TNFα-inhibitor (TNFi) therapy is effective in controlling several rheumatic diseases and has been shown to reduce pain in patients with arthritis. Opioids are often prescribed for chronic pain, a common issue in inflammatory joint disease.Objectives:To explore the impact of the initiation of TNFi therapy as a first-line biologic disease-modifying anti-rheumatic drug (DMARD) on the prescription rates of opioids in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and undifferentiated arthritis (UA) in Iceland.Methods:All patients receiving biologic DMARD therapy for rheumatic diseases in Iceland are registered in a nationwide database (ICEBIO). The Icelandic Directorate of Health operates a Prescription Medicines Register that includes over 90% of all drug prescriptions in Iceland. The study group included patients with RA, PsA, AS, and UA registered in ICEBIO and for each of them five randomly selected comparators from the general population matched on age, sex, and calendar time. On February 1st2016 we extracted data on all filled opioid analgesic prescriptions two years before and two years after the date of TNFi initiation.Results:Data from 359 RA, 217 AS, 251 PsA and 113 UA patients and 4700 comparators were collected. In total, 75% of patients compared to 43% of comparators received ≥1 opiate prescription during the study period. The proportion of patients using opioids (regardless of dose) two years prior to TNFi initiation was 41%, increasing to 49% the following year. After TNFi initiation the proportion returned to 40% (Figure 1). Despite this, the mean yearly opiate dose used by the patients followed a rising trajectory throughout the study period (Figure 2). In total, patients were prescribed nearly 6 times more opioids than the comparators, corresponding to a bootstrapped mean (95% CI) dose of 818 (601-1073) mg MED per patient and year compared to 139 (111-171) mg for comparators.Figure 1.Percental distributions of opioid analgesic use by dose (according to dispensed prescriptions) among patients with inflammatory arthritis (A) and matched comparators (B). All doses are oral morphine equivalent dose (MED) in milligrams.Figure 2.Bootstrapped mean oral morphine equivalent dose per person per year for patients with inflammatory arthritis (above) and age and sex matched comparators (below). Box edges represent 25-75thpercentiles and whiskers 95% confidence intervals.Conclusion:Three out of four patients with inflammatory arthritis in Iceland use opioid analgesics in the two years prior to and/or after the initiation of TNFi therapy and the mean doses were significantly higher than in matched comparators. The proportion of patients receiving opioids increased before TNFi therapy and then decreased again to the previous level. The initiation of the first-line TNFi did not reduce opioid consumption by dose at the group level. On the contrary, there was a trend towards increasing doses over time in both patients and comparators, possibly reflecting the development of opiate tolerance.Table 1.Baseline demographic data. Mean ± SD unless specified. * defined from diagnosis to baselAll patientsRheumatoid arthritisPsoriatic arthritisAnkylosing spondylitisUndifferentiated arthritisTotal n (%)940 (100)359 (38)251 (27)217 (23)113 (12)Age (years)49 ± 1453 ± 1449 ± 1343 ± 1344 ± 15Disease duration (years)*7.8 ± 8.58.2 ± 8.27.4 ± 7.88.3 ± 10.26.3 ± 6.6Female58%73%59%34%52%Disclosure of Interests:Olafur Palsson: None declared, Thorvardur Love: None declared, Johan K Wallman Consultant of: Consultant for AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma., Meliha C Kapetanovic: None declared, Petur S Gunnarsson: None declared, Björn Gudbjornsson Speakers bureau: Novartis and Amgen


2019 ◽  
Vol 8 (11) ◽  
pp. 1859
Author(s):  
Bossennec ◽  
Rodriguez ◽  
Hubert ◽  
Di-Roio ◽  
Machon ◽  
...  

Objectives: Th1.17 are highly polyfunctional, potentially harmful CD4+ effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients. Methods: In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions. Results: We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73+ Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation. Conclusion: Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ali S. F Sheikh ◽  
Sagar G Srivastva ◽  
Fiona Wood

Abstract Background Psoriatic arthritis requires early recognition and treatment for prevention of disease progression. Conventional disease modifying drugs are first-line agents followed by biologic DMARDs for patients with active disease. TNF-alpha blockers are first line biologic agents in the UK. Th17 inhibitors are used since the elucidation of Th17 pathway. Safety and efficacy profiles of biologic agents inhibiting the Th17 pathway, including secukinumab (IL-17A) and ustekinumab (IL-12/23p40) have been studied. Methods We report a case of carcinoid syndrome in a lady on etanercept for psoriatic arthritis, carcinoid as a potential TNF alpha side effect. We also report safety of Th17 (secukinumab) inhibitors in the patient to date (>1 year). Results A female with a history of acne rosacea, was diagnosed with psoriatic arthritis in 2000 age 32. Initial sulphasalazine failed, then received methotrexate until 2011, when her arthritis flared. She was commenced on etanercept which proved effective. After 4 years of etanercept and methotrexate, her liver profile became deranged. Investigations off treatment included ultrasound abdomen demonstrating a liver mass, which resembled focal nodular hyperplasia on magnetic resonance imaging. Further screening revealed high urinary 5HIAA (527 umol/24h) and raised chromogranin A & B levels (1574 pmol/L and 373 pmol/L respectively). She had no symptoms suggestive of carcinoid, although facial flushing could have been camouflaged by her rosacea. Octreotide scan was positive, CT enterogram showed a distal ileal neuroendocrine tumour with adjacent lymphadenopathy. She underwent right hemihepatectomy and hemicolectomy. Her liver profile deteriorated again on methotrexate, leflunomide was ineffective. In November 2017 she was started on ustekinumab, which was ineffective and was withdrawn after 8 months. There was no alteration in carcinoid blood markers and no CT changes. In July 2018, she was commenced on secukinumab, which has allowed reduction in steroids. The patient is aware of lack of safety data in her circumstances. Regular surveillance has shown no recurrence of carcinoid with serial negative 5HIAA and chromogranin levels. There are no progressive CT changes at 1 year. Conclusion This is a case of carcinoid tumour occurring on TNF-alpha blockers and may represent a rare complication. Screening biomarkers including 5HIAA and chromogranin levels can be useful if disease is suspected. We could not find other similar case reports to guide further management. Within time limited data available - ustekinumab had no effect on the carcinoid. Th17 inhibitors can be safe options for treating psoriatic arthritis and psoriasis with highly sustained efficacy and favourable safety profile seen in large clinical trials. In this case, after > one year of secukinumab treatment - there is no adverse effect on carcinoid syndrome. Disclosures A.S.F. Sheikh None. S.G. Srivastva None. F. Wood None.


2018 ◽  
Vol 14 (2) ◽  
pp. 21-35 ◽  
Author(s):  
N. A. Avksentyev ◽  
M. V. Zhuravleva ◽  
E. M. Pazukhina ◽  
A. V. Snegovoy ◽  
M. Yu. Frolov

Background.Breast cancer is the most common malignant tumor and accounts for the most number of cancer-related deaths among Russian women. Combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor ribociclib and aromatase inhibitor is approved for the first-line treatment of postmenopausal women with HR-positive HER2-negative advanced breast cancer.Objective:to conduct pharmacoeconomic evaluation of using ribociclib + aromatase inhibitor for the first-line treatment of HR-positive HER2- negative advanced breast cancer from the Russian healthcare system perspective.Materials and methods.The comparator was palbociclib + aromatase inhibitor, because ribociclib and palbociclib have similar mechanism of action and are the only available CDK4/6 inhibitors that could be used for treatment of HR-positive HER2-negative advanced breast cancer in Russia. Using clinical trials data and published results of matching adjusted indirect comparison (MAIC), we proposed Markov chain model of breast cancer progression and estimated direct medical costs associated with two considered options (first and subsequent lines of drug therapy, adverse events treatment, inpatient and outpatient care). Budget impact and cost-effectiveness analyses were conducted. Mean duration of treatment in the model was 21,9 and 20,2 months on ribociclib and palbociclib for five year time horizon respectively.Results and conclusion.Monthly medication costs of ribociclib (270 814.18 RUB) were 9 % less than for palbociclib (296 517.21 RUB). Driven by less monthly medication costs and potential of cost reduction due to dose reduction, five-year total medical per patient costs for ribociclib were 4 991 168 RUB, which were 1 162 666 RUB or 19 % less than for palbociclib. Ribociclib also had better (lower) cost/effectiveness ratio (1 244 906 vs 1 595 867 RUB per life year). As the result, ribociclib was considered a cost-saving option. If 8 162–8 270 women receive ribociclib, public healthcare expenditures will decrease by 20.1 billion RUB (21 %) within 3 years, compared to palbociclib.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1665.2-1666
Author(s):  
J. Arroyo Palomo ◽  
I. Del Bosque Granero ◽  
A. Corral Bote ◽  
B. A. Blanco Cáceres ◽  
J. Bachiller-Corral

Background:Psoriatic arthritis (PsA) covers a wide spectrum of disease manifestations, including arthritis, enthesitis, dactylitis and axial spondylitis. This range of symptoms presents a challenge to the treating physician. Biologic disease-modifying antirheumatic drugs (bDMARDs) have proven effective through randomized clinical trials; and most international PsA guides include them as main option upon first-line treatment failure. However, studies regarding drug efficacy after bDMARD switching are scarce, lower response rates and drug survival on consecutive lines has been explored in previous research.Objectives:To assess bDMARDs survival after first-line failure in PsA patients treated in a third-level hospital and to determine baseline clinical and laboratory parameters associated with drug survival.Methods:We conducted a retrospective, single-centre study. 47 patients who received a second-line bDMARD were included, with diagnosis of PsA according to the criteria of an expert rheumatologist. All patients were studied according to a standard protocol. Data regarding bDMARD prescribed, baseline characteristics, axial or peripheral involvement and immunological profile (included both HLA-B27 and HLA-Cw6) were extracted. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at bDMARD start were included, as well. Kaplan-Meier, log-rank analyses and Cox regression models were applied.Results:Of 47 patients receiving a second bDMARD, 55,3% (26) were female and mean (S.D.) age was 40,6 (12,52) years. Median (interquartile range) disease duration was 10,1 (3,7-14,8) years. Prescribed drugs were Adalimumab (ADL) (36,2%, 17), Etanercept (ETN) (27,6%, 13), Infliximab (IFX) (6,4%, 3), Golimumab (GOL) (10,6%, 5), Certolizumab (CTZ) (4,3%, 2), Secukinumab (SCK) (8,5%, 4) and Apremilast (APR) (6,4%, 3). 42,3% cases suffered from axial involvement, rest of the sample (57,6%) presented a pure peripherical form of PsA. HLA-B27 and -Cw6 were assessed in 80,9% (38) and 68,1% (32), respectively; of whom, HLA-B27 carriers were 10,5% and HLA-Cw6 positive, 46,9%. Mean CRP level was 10,25 mg/L and mean ESR was 23,17 mm. Patients showed mean and median global drug retention of 44,57 (29,8-59,3) and 23 months. At 12-month visit, drug survival was 70%, 47% at 24 months, and 33% at 4 years from onset. Mean drug persistence by bDMARD prescribed was: ADL, 62,1 months; ETN, 51,9 months; IFX, 39 months; GOL, 22,8 months; CTZ, 9,5 months; SCK, 13,5 months; and APR, 16,3 months. Through log-rank analyses, differences in drug retention were investigated by several variables. Female sex (30,35m, 16,5-44,2 m.) was identified as statistically significant different than male patients (62,5m, 35,6-89,4m, p=0,021). Although not significant, other differences were remarkable: non-axial involvement, HLA-Cw6 negativity, HLA-B27 positivity and CRP level over 5 mg/L. No differences were found between altered and normal ESR patients.Conclusion:Second-line bDMARD survival is lower in female PsA patients, according to our data and previous bibliography. Despite our reduced sample and possible bias, non-axial involvement, absence of HLA-Cw6, presence of HLA-B27 and higher levels of CRP at biologic onset might be predictors of better drug persistence. Further investigations are required on this field.References:[1]Glintborg B et al. Clinical Response, Drug Survival, and Predictors Thereof Among 548 Patients With Psoriatic Arthritis Who Switched Tumor Necrosis Factor α Inhibitor Therapy. Results from the Danish Nationwide DANBIO Registry. Arthritis Rheum 2013:65(5):1213-23.[2]Stober C et al. Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis. Rheumatology (Oxford) 2018:57(1):158-163.Table 1. Kaplan–Meier survival analysis of persistence according to sex.Table 2. Kaplan Meier survival analysis of persistence according to HLA-Cw6.Disclosure of Interests:None declared


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