Maintenance Treatment Of Adults Research Articles

Infliximab (Remsima SC)

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses Description infliximab (Remsima SC), 120 mg/mL solution for subcutaneous injection. Indication: Maintenance treatment of adults with moderately to severely active Crohn disease who have had an inadequate response to or were intolerant of conventional therapy. Remsima SC should be used only as maintenance therapy after the completion of an induction period with IV infliximab.

Infliximab (Remsima SC)

We recommend that Remsima SC be reimbursed by public drug plans as maintenance treatment for adults with moderately to severely active ulcerative colitis (UC) whose disease has had an inadequate response, or who were intolerant, to conventional therapy if certain conditions are met. Remsima SC maintenance treatment should only be covered to treat adults with moderately to severely active UC whose disease has had an inadequate response, or who are intolerant, to conventional therapy. Patients are required to achieve a clinical response to induction therapy with infliximab IV at week 10 of treatment to continue with Remsima SC as maintenance therapy. Remsima SC should only be reimbursed if prescribed by a physician experienced in diagnosing and managing UC and should not be reimbursed if used in combination with other advanced therapies for UC. The cost of Remsima SC should not exceed the drug program cost of treatment with the least costly biologic therapy reimbursed for the treatment of UC.

Infliximab (Remsima SC)

We recommend that Remsima SC be reimbursed by public drug plans as maintenance treatment for adults with moderately to severely active Crohn disease (CD) whose disease has had an inadequate response, or who were intolerant to, conventional therapy if certain conditions are met. Remsima SC maintenance treatment should only be covered to treat adults with moderately to severely active CD whose disease had an inadequate response, or who are intolerant, to conventional therapy. Patients are required to achieve a clinical response to induction therapy with infliximab IV at week 10 of treatment to continue with Remsima SC as maintenance therapy. Remsima SC should only be reimbursed if prescribed by a physician experienced in diagnosing and managing CD and should not be combined with a biologic or Janus kinase (JAK inhibitor) treatment for CD. The cost of Remsima SC should not exceed the drug program cost of treatment with the least costly biologic therapy reimbursed for the treatment of CD.

Tezepelumab (Tezspire)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses Tezepelumab (Tezspire), 210 mg, 110 mg/mL solution for subcutaneous injection.
 Indication (proposed): indicated as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma.

Alpha1-Proteinase Inhibitor (Human) (Zemaira)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses alpha1-proteinase inhibitor (human) (Zemaira), 60 mg/kg body weight administered by IV infusion once weekly.
 Indication: Maintenance treatment of adults with severe alpha1-proteinase inhibitor deficiency and clinical evidence of emphysema.

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer.

Olaparib (Lynparza®) is a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor approved for first-line maintenance treatment in adults with advanced ovarian cancer who are in complete or partial response to first-line, platinum-based chemotherapy. Originally approved as monotherapy, olaparib is also approved to be administered in combination with bevacizumab in patients whose cancer is associated with homologous recombination deficiency (HRD), defined by either a BRCA1/2 mutation and/or genomic instability. In phaseIII trials, olaparib monotherapy significantly improved progression-free survival (PFS) relative to placebo (SOLO-1), as did olaparib plus bevacizumab relative to placebo plus bevacizumab (PAOLA-1), in patients with advanced ovarian cancer who had responded to platinum-based chemotherapy. In PAOLA-1, improvements in PFS with olaparib plus bevacizumab were not seen in patients with HRD-negative tumours relative to placebo plus bevacizumab. Both olaparib monotherapy and olaparib in combination with bevacizumab had generally manageable tolerability profiles. Olaparib, alone or in combination with bevacizumab, is a useful option for the first-line maintenance treatment of adults with HRD-positive, advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line, platinum-based chemotherapy.

Maintenance Treatment With Long-Acting Injectable Antipsychotics for People With Nonaffective Psychoses: A Network Meta-Analysis.

This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses. The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone). LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

Treatment of Patients with Recently Exacerbated Schizophrenia with Paliperidone Palmitate: A Pilot Study of Efficacy and Tolerability.

BackgroundPaliperidone palmitate is a long-acting, second-generation antipsychotic (SGA) indicated for the treatment of acute exacerbations and maintenance treatment of adults with schizophrenia. This study addressed the response to paliperidone palmitate in Latin American patients with acute symptoms and recently diagnosed schizophrenia.ObjectiveExplore the efficacy and tolerability of paliperidone palmitate administered once a month for 4 months in patients with acute phase and recent diagnosis (within 1–6 years) of schizophrenia in 3 Latin American countries.MethodsThis was a non-randomized, open-label, multicenter study with paliperidone palmitate injected intramuscularly in the deltoid muscle at an initial loading dose of 150 mg eq. (234 mg) on day 1 and 100 mg eq. (156 mg) on day 8 (± 4 days). The recommended maintenance dose was 75 mg eq. (117 mg) from day 36 to day 92. Efficacy was evaluated with PANSS and CGI-S. The last observation carried forward (LOCF) was used for efficacy analysis for imputation of missing data; no adjustments were made for multiplicity. Adverse events were evaluated during treatment.ResultsThe patient retention rate was 84.0% (144 patients received study drug; 121 finished the study). The percentage of patients with a reduction of at least 30% in PANSS total score compared to baseline gradually increased during the study, and at the end, 78.4% of patients showed response. The PANSS total score and CGI-S scores decreased significantly from baseline to LOCF endpoint (P <0.0001 for both); significant reduction in PANSS total score was observed at day 8 and persisted to the end of the study. Most common adverse events were muscle rigidity (11.8%), akathisia (11.1%), injection-site pain (7.6%), weight gain (7.6%), and insomnia (7.6%).ConclusionPaliperidone palmitate was efficacious in Latin American patients studied with an acute exacerbation and recent diagnosis of schizophrenia, and no new safety signals were identified.

P0434COST-EFFECTIVENESS OF MAINTANCE THERAPY WITH AZATHIOPRIME VERSUS RITUXIMAB (TAILORED OR FIXED-SCHEDULE) IN ADULTS WITH GENERALIZED ANCA VASCULITIS IN COLOMBIA

Abstract Background and Aims Azathioprine has been for decades the drug of choice for maintenance therapy in patients with generalized ANCA vasculitis in remission. However, recent studies show that rituximab, a high-cost biological agent, which can be administrated in two different schedules, might be more effective, so it is necessary to know the cost- effectiveness. Our goal was to compare the cost-effectiveness of the 3 maintenance schemes: standard therapy with azathioprine; fixed-dose rituximab and rituximab tailored according to CD19 lymphocyte level and ANCA titres, from the perspective of the Colombian healthcare system. Method We designed a 5-year annual cycle Markov model with the following stages: remission, minor relapse, mayor relapse and death. Transition probabilities were obtained from a systematic review of the literature (Scopus and Pubmed). Following national guidelines for economic studies, costs (in 2018, 1 euro = 3489 Colombian pesos) were estimated based on national drug registries, and official tariff manuals for procedures and other resources. Main outcome was quality-adjusted life years (QALY), using lupus nephropathy as a proxy; values were obtained from Tufts CEA Registry and validated by local expert panel through a modified Delphi technique. Cost-effectiveness threshold was three-times per capita GDP (16.872 euros). Discount rate was 5%. Univariate and probabilistic sensitivity analyses were performed. Results Overall discounted 5-years costs were € 1149 for azathioprine; € 4025 for tailored rituximab and € 5221 for fixed rituximab. QALY gains were 2.94, 3.63 and 3.64, respectively. Both tailored and fixed rituximab were cost-effective (cost per QALY gained: € 4168 and € 5817 respectively), but tailored dosing was preferable due to its lower cost. Sensitivity analyses did not modify these results significantly. Conclusion To our knowledge this is the first economic evaluation that compare azathioprine with tailored and fixed rituximab regimens as a vasculitis maintenance treatment in adults with ANCA generalized. Due to its lower effectiveness azathioprine should not be the first line of treatment. Tailored rituximab should be a better option than fixed schedule due to its lower cost with similar effectiveness.

Olaparib Approved for Metastatic Pancreatic Cancer.

Olaparib (Lynparza) is now approved for maintenance treatment in adults with deleterious or suspected deleterious germline BRCA-mutated metastatic pancreatic adenocarcinoma.

OP23 Efficacy and safety of vedolizumab SC in patients with moderately to severely active Crohn’s disease: Results of the VISIBLE 2 study

Abstract Background Vedolizumab (VDZ) is a gut-selective, humanised, monoclonal α 4β 7 integrin antibody for the treatment of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). VDZ is currently an intravenous (IV) therapy; a subcutaneous (SC) formulation is under development to provide patients with an alternative route of administration for maintenance treatment for UC and CD. Here we present the first data from the phase 3 study of VDZ SC maintenance treatment in CD. Methods VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a randomised, double-blind, placebo (PBO)-controlled phase 3 trial of VDZ SC as maintenance treatment in adults with moderately to severely active CD. Patients (n = 644) received open-label VDZ 300mg IV induction therapy at Weeks 0 and 2. At Week 6, clinical responders (defined as patients with a ≥70-point decrease in CD Activity Index [CDAI] from baseline) were randomly assigned to receive vedolizumab SC (108 mg every 2 weeks [Q2W]), or placebo (Q2W) for up to 52 weeks. The primary endpoint was clinical remission at Week 52 (defined as CDAI score ≤150). Rank-ordered secondary endpoints were enhanced clinical response at Week 52 (a drop of ≥100 in CDAI score), corticosteroid (CS)-free clinical remission at Week 52, and clinical remission at Week 52 in anti-tumour necrosis factor (TNF)-naïve patients. Finally, VDZ immunogenicity and predefined adverse events of special interest were assessed. Results Patients who responded to VDZ IV induction at Week 6 (n = 409) were randomised to VDZ SC (n = 275) or PBO (n = 134) maintenance and received at least 1 dose of study drug; 61% and 53%, respectively, were previously exposed to anti-TNF therapy. At Week 52, 48.0% of patients on VDZ SC vs. 34.3% on PBO were in clinical remission (p = 0.008, Figure). Enhanced clinical response at Week 52 was reached by 52.0% vs. 44.8% of patients on VDZ SC vs. PBO, respectively (p = 0.167). Among patients on concomitant CS at baseline (VDZ SC, n = 95; PBO, n = 44), 45.3% receiving VDZ SC vs. 18.2% receiving PBO achieved CS-free clinical remission at Week 52. Of anti-TNF-naïve patients (VDZ SC, n = 107; PBO, n = 63), 48.6% vs. 42.9% were in clinical remission at Week 52 in the VDZ SC and PBO arms, respectively. Injection-site reactions were reported for &amp;lt;3% of patients treated with VDZ SC. Serious infections, malignancy, and liver injury were ≤5% for both arms. Anti-VDZ antibodies were detected in 7 (2.5%) patients treated with VDZ SC arm; 4 of 7 patients developed neutralising antibodies. No new safety signals were observed. Conclusion Among VDZ IV induction responders, significantly more patients on maintenance VDZ SC than PBO achieved clinical remission at Week 52. The safety findings with VDZ SC remain in line with the known safety profile of VDZ IV in patients with CD.

634 Transitioning From Vedolizumab IV to Vedolizumab SC in Patients With Ulcerative Colitis: Results From the VISIBLE Program

INTRODUCTION: Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is approved as an intravenous (IV) formulation to treat ulcerative colitis (UC). In the first completed study with a new VDZ subcutaneous (SC) formulation (VISIBLE 1, NCT02611830, a randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial assessing VDZ SC as maintenance treatment in adults with moderately to severely active UC), VDZ SC demonstrated statistically significant efficacy superior to placebo as maintenance treatment in patients with UC who had achieved a response to VDZ IV induction. The VDZ SC clinical program also includes an open-label extension (OLE, NCT02620046, ongoing). Analyses across these 2 studies allow for evaluation of efficacy when transitioning from VDZ IV to VDZ SC in patients who achieved clinical benefit with VDZ IV treatment for varying durations. METHODS: Efficacy of VDZ SC treatment after initial VDZ IV (300 mg) infusion was evaluated in 3 groups according to the duration of VDZ IV treatment before transitioning to VDZ SC (108 mg; Figure 1): (A) After 2 VDZ IV infusions (Week [W] 0 and 2) in patients who achieved clinical response at W6 and were randomized to VDZ SC maintenance treatment in VISIBLE 1; (B) After 3 VDZ IV infusions in patients who did not achieve clinical response at W6 who received a third VDZ IV infusion at W6 and had clinical response at W14 in VISIBLE 1 before enrolling in the OLE and transitioning to VDZ SC; (C) After 8 VDZ IV infusions (W0, W2, W6, and every 8 weeks thereafter until W52) in patients randomized to VDZ IV maintenance treatment in VISIBLE 1, completed 52 weeks of VDZ IV treatment, and transitioned to VDZ SC in the OLE. RESULTS: Patients who transitioned to VDZ SC after 2 infusions of VDZ IV (N = 106) had a clinical remission rate of 46.2% and a clinical response rate of 65.1% at W52. Among patients who received 3 VDZ IV infusions before transitioning to VDZ SC (N = 107), 39.2% achieved clinical remission and 48.0% achieved clinical response at W54 (14 weeks of IV; 40 weeks of SC). For patients who transitioned to VDZ SC after receiving 8 VDZ IV infusions over 52 weeks in VISIBLE 1 (N = 35), clinical remission and clinical response rates (both 76.9%) were maintained during the OLE on SC through W24 (Tables 1 and 2). CONCLUSION: Transitioning from initial VDZ IV treatment to VDZ SC maintenance treatment retains therapeutic benefit, independent of initial vedolizumab IV treatment duration.

Dopamine Receptor Partial Agonists for the Treatment of Bipolar Disorder.

Bipolar disorder is a chronic, disabling, and costly illness with frequent relapses and recurrences, high rates of co-morbid conditions, and poor adherence to treatment. Mood stabilizers and antipsychotics are the cornerstones of treatment. Dopamine receptor partial agonists are a novel class of antipsychotic agents with original pharmacodynamic properties. Among them, two have been approved by the US Food and Drug Administration for the treatment of bipolar disorder. Aripiprazole (oral formulation) has been approved as monotherapy for the treatment of manic/mixed episodes in adult and pediatric populations and for maintenance treatment in adults, and as adjunctive treatment to mood stabilizers, for the acute treatment of manic/mixed episodes and for maintenance in adults. An intramuscular formulation of aripiprazole has been approved for the treatment of agitation in mania and a long-acting injectable formulation has been approved as maintenance treatment. In the USA, cariprazine has been approved as monotherapy for the acute treatment of manic/mixed as well as bipolar depressive episodes. Brexpiprazole is not yet approved to treat bipolar disorder. The evidence supporting these indications is reviewed via an analysis of clinical registration trials as well as additional studies, on the basis of a systematic literature search. Further studies dealing with other aspects of bipolar illness are also presented. Aripiprazole and cariprazine are efficacious and generally well tolerated agents that have shown cost effectiveness, and may therefore enrich our therapeutic armamentarium for bipolar illness. Brexpiprazole, which displays an overall promising tolerability profile, deserves further efficacy studies.

PCN68 COST EFFECTIVENESS OF CIMAVAX EGF VS. STANDARD-OF-CARE AS MAINTENANCE TREATMENT FOR ADVANCED NSCLC THAT EXPRESSES HIGH LEVELS OF EGF IN COLOMBIA

The aim of the study was to evaluate the cost effectiveness of CIMAvax-EGF, compared with standard-of-care (SoC) as maintenance treatment in patients with non-small-cell lung cancer (NSCLC) that expresses high levels of EGF, from a Colombia third-party public healthcare payer perspective. We conducted a markov model with a cycle length of three months and a time horizon of four years. Parametric survival models were fitted to Kaplan–Meier estimates of overall survival from a randomized clinical trial (patients aged ≥18 years with stage IIIB – IV NSCLC, ECOG 0-2, who received systemic chemotherapy). Progression free survival were validated from registry data. Costs (COP, year 2016 values) for drug acquisition/administration and clinical management were included. Costs and outcomes were discounted at 5% per year. For the base-case scenario data was evaluated for patients with squamous NSCLC. An alternative scenario was evaluated for all patients with NSCLC comparing CIMAvax-EGF to other maintenance therapies. A deterministic and probabilistic sensitivity analyses were performed. In the base-case scenario, CIMAvax resulted in an expected gain of survival. The incremental cost per LY gain was COP 30.132.000/LY. The cost-effectiveness threshold in Colombia established for the year 2016 is approximately COP 43,500,000 / LY. So, it is considered that CIMAvax-EGF is a cost-effective therapy. The sensitivity analysis showed that the cost of second-line therapy is the variable that most affects the mode. In 95% of the cases evaluated, CIMAvax-EGF was the most cost-effective therapy. CIMAvax-EGF is a cost-effective option compared with SoC as maintenance treatment in adults with NSCLC expressing high levels of EGF.

Cariprazine for acute and maintenance treatment of adults with schizophrenia: an evidence-based review and place in therapy.

Cariprazine is an oral antipsychotic approved in the US and EU for the treatment of schizophrenia. Cariprazine differs from other antipsychotics in that it is a dopamine D3- and D2-receptor partial agonist, with tenfold higher affinity for D3 receptors than for D2 receptors. Cariprazine is metabolized in two steps by CYP3A4 to didesmethyl-cariprazine (DDCAR). DDCAR has a long half-life of 1–3 weeks and is the predominant circulating active moiety. Efficacy and safety in persons with acute schizophrenia were assessed in four similarly designed, short-term, randomized, placebo-controlled clinical trials in nonelderly adults, with three studies considered positive and yielding a number needed to treat vs placebo for response (change from baseline ≥30% in Positive and Negative Syndrome Scale total score) of ten for the approved dose range of cariprazine 1.5–6 mg/day. The most common adverse reactions were extrapyramidal symptoms (15% and 19% for 1.5–3 and 4.5–6 mg/day, respectively, vs 8% for placebo) and akathisia (9% and 12.5% for 1.5–3 and 4.5–6 mg/day, respectively, vs 4% for placebo). For the approved dose range, rates of discontinuation because of an adverse event were lower overall for patients receiving cariprazine vs placebo (9% vs 12%). Weight and metabolic profile appear favorable. Cariprazine does not increase prolactin levels or prolong the electrocardiographic QT interval. Cariprazine has also been found to be effective for the maintenance treatment of schizophrenia by delaying time to relapse when compared with placebo (HR 0.45). A 26-week randomized clinical trial evidenced superiority of cariprazine over risperidone for the treatment of predominantly negative symptoms in patients with schizophrenia. Cariprazine is also approved in the US for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and is being studied for the treatment of bipolar I depression and major depressive disorder.

Once-daily triple therapy inhaler for COPD

▼Trelegy Ellipta (GSK) is a dry powder inhaler containing fluticasone furoate (inhaled corticosteroid [ICS]), vilanterol trifenatate (long-acting beta2 agonist [LABA]) and umeclidinium bromide (long-acting muscarinic antagonist [LAMA]).1 It is licensed...

964P - Modeling and impact of organ function on the population pharmacokinetics (PK) of niraparib, a selective poly (ADP-Ribose) polymerase (PARP)-1 and -2 inhibitor

Background: Niraparib (ZEJULA™) is a selective PARP-1 and -2 inhibitor approved for maintenance treatment in adults with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. We developed a population PK (PPK) model for niraparib and determined the impact of hepatic and renal organ impairment on niraparib exposure. Methods: Data from the phase 1 dose escalation and expansion (dose ranging from 30 to 400 mg once daily [qd]) and phase 3 ENGOT-OV16/NOVA (300 mg qd) studies were modeled using a compartmental population approach within nonlinear mixed-effects modeling (NONMEM). Patients (pts) who received a dose of niraparib were included in the PK analysis. The PPK base model was built using NONMEM techniques from the phase 1 study. The impact of pt variables (age, race, ethnicity, body weight), renal impairment (normal, mild, or moderate, based on serum creatinine clearance) and hepatic function (baseline serum alanine and aspartate aminotransferase, albumin, total bilirubin) on niraparib PK parameters was evaluated. A step-wise elimination procedure for each covariate was used to develop the final model. Model evaluation was performed via a visual predictive check. Results: 512 pts (33–83 years old) were available for PK analysis (4109 measurements) from the phase 1 (n = 104) and phase 3 (n = 408) studies. A 2-compartment model (2CM) with first-order absorption and elimination best described the niraparib PK. In the base model, the typical value for niraparib apparent clearance was 16.2 L/h, with interindividual variability of 52.6%. The estimated volume of distribution was 1074 L (290 L central and 784 L peripheral compartment. Model diagnostics showed good agreement between predicted and observed individual niraparib plasma concentrations. No patient variables impacted niraparib PK. Neither the mild to moderate renal impairment nor the mild hepatic impairment significantly altered niraparib PK. Conclusions: Niraparib disposition was best described by a 2-compartment model with moderate to high interindividual variability. Mild to moderate organ impairment did not significantly impact niraparib PK; no dose adjustments are recommended. Clinical trial identification: NCT01847274 Legal entity responsible for the study: Tesaro, Inc. Funding: Tesaro, Inc. Disclosure: Z-Y. Zhang, X. Wang, J. Wang, V. Kansra: Employment: Tesaro; Stock: Tesaro. H.S. Pentikis: Advisory board or board of directors: Tesaro; Consulting: Tesaro.

Can drug interaction be useful? Case report of a schizophrenic patient treated with paliperidone long-acting injection

IntroductionIntramuscular paliperidone palmitate (PLAI) is a long-acting atypical anti-psychotic approved in Romania for the maintenance treatment of adults with schizophrenia.ObjectivesTo determine the efficacy and tolerability of PLAI in a non-compliant patient with previously very low tolerability to oral anti-psychotics. The patient had been on risperidone long acting injection (RLAI) and had significant adverse events (i.e. tremor, akatisia) which persisted even when treated with the lowest dose of PLAI: 50 mg.AimsSince the efficacy of PLAI was good, and since a lower dose (than 50 mg of PLAI) is not available in Romania, we tried different ways to lower plasma concentration (PC) of the anti-psychotic because the patient presented clinically significant adverse effects (AE).MethodsInitially the time between the injections was extended at maximum recommended (35 days), with a slight effect, then an off label treatment was associated in order to lower the PC of PLAI. We used 300 mg of carbamazepine long acting, that may lower the PC of PLAI up to 30%. For the evaluation of the efficacy and tolerability, we applied: the clinical evaluation, the positive and negative syndrome scale, the Barnes Akathisia rating scale, the Simpson-Angus Scale and the abnormal involuntary movement scale.ResultsAfter using the above mentioned, strategies, the one that had indeed good results on reducing AE, with no alteration of the psychic status of the patient, was the association of carbamazepine.ConclusionsIn clinical practice, some off label medication associations may be salutary!Disclosure of interestThe authors have not supplied their declaration of competing interest.

Aclidinium bromide/formoterol fumarate dry-powder inhaler: a guide to its use in chronic obstructive pulmonary disease in the EU

The use of a dry-powder inhaler containing both aclidinium bromide (a long-acting antimuscarinic agent) and formoterol fumarate (a long-acting β2-selective adrenoreceptor agonist) [Duaklir® Genuair®] is an effective, convenient and well-tolerated option for the maintenance treatment of adults with chronic obstructive pulmonary disease (COPD). Aclidinium/formoterol 340/12 µg twice daily provided rapid and durable improvements in lung function, as well as improvements in COPD control, symptoms and health status outcomes, in clinical trials in patients with stable moderate to severe COPD.

Umeclidinium/vilanterol: a review of its use as maintenance therapy in adults with chronic obstructive pulmonary disease.

Umeclidinium/vilanterol (Anoro(®) Ellipta™; Laventair™) is an inhaled fixed-dose combination of a long-acting muscarinic receptor antagonist and a long-acting β2-adrenoceptor agonist. It is available in several countries, including Japan, the USA, Canada and those of the EU, where it is indicated for oral inhalation in adults with chronic obstructive pulmonary disease (COPD). Umeclidinium/vilanterol is administered once daily using the Ellipta™ multi-dose dry powder inhaler, which is regarded as easy to use. Umeclidinium/vilanterol (62.5/25µg once daily, equivalent to a delivered dose of 55/22µg once daily) was effective and well tolerated in adult patients with COPD participating in large, multicentre trials of up to 24weeks' duration. Umeclidinium/vilanterol improved pulmonary function to a significantly greater extent than placebo and each of the individual components. Moreover, umeclidinium/vilanterol was significantly more effective than once-daily tiotropium bromide monotherapy and a twice-daily fixed combination of salmeterol/fluticasone propionate at improving pulmonary function. Umeclidinium/vilanterol also had beneficial effects on dyspnoea, use of rescue medication, exacerbations, health-related quality of life and, in one study, exercise endurance. Umeclidinium/vilanterol is generally well tolerated in patients with COPD, with the most common adverse events in clinical trials being headache and nasopharyngitis. Umeclidinium/vilanterol was not associated with a clinically relevant increased risk of cardiovascular adverse events in patients with COPD, when data from several clinical trials were pooled. Thus, inhaled umeclidinium/vilanterol extends the treatment options currently available for the maintenance treatment of adults with COPD and has the convenience of once-daily administration.