AB0217 NON MEDICAL SWITCH FROM ETANERCEPT ORIGINATOR TO BIOSIMILAR GP2015 IN PATIENTS WITH CHRONIC INFLAMMATORY ARTHROPATHIES

Background:In the last decades, new biologic drugs were introduced for the treatment of chronic inflammatory arthropathies, progressively leading to a relevant increase of medical costs. However, the introduction of biosimilars (biologic molecules similar to branded drugs with expired patent) permitted to optimize the financial resources. The non-medical switch (NMS) is the switch from a biologic originator to a biosimilar agent for economic reasons only, on the basis of the substantial equivalence as regards efficacy and safety between originator and biosimilar drugs.In literature, several evidences from clinical trials and registry studies showed that the switch from etanercept originator to biosimilar SB4 was safe [1]. Instead no sufficient data may be found regarding the biosimilar GP2015.Objectives:We aimed to evaluate efficacy, safety, and retention rate in a series of patients with chronic arthritis treated with etanercept originator who underwent to NMS towards the ETN biosimilar GP2015.Methods:From March to June 2020, all patient referred in our Centre affected by rheumatoid arthritis (RA), psoriatic arthritis (PA) and axial spondyloarthritis (axSpA) treated with etanercept originator and in remission/low disease activity for at least 6 months underwent to NMS. Data on disease activity (DAS28-PCR/CDAI/SDAI; DAPSA; BASDAI), eventual adverse events and causes of withdrawal of therapy were collected at 2, 4 and 6 months after the switch.Results:We recruited 71 consecutive patients (M/F: 24/47; mean age 55,8± 11,1 years; 39 RA; 15 PA; 17 axSpA; mean duration therapy 7.3±3.8 years). Disease activity was unchanged for almost all patients after 6 months from the switch (median ΔDAS28-PCR/CDAI/SDAI: 0,1/0/0,5; median ΔDAPSA: 0; median ΔBASDAI: 0) Moreover, the 6-month retention rate was 97.2%. Only 2 patients (2.8%) switched back to the originator due to loss of efficacy in one case and adverse events in the second case (paraesthesia, headache, dizziness and worsening of arthralgia).Conclusion:Our study confirmed that the NMS from ETN originator to GP2015 represents a safe practice that maintains the efficacy of the current treatment.References:[1]Glintborg B, AG, Omerovic E, et Al. To switch or not to switch: results of a nationwide guideline of mandatory switching from originator to biosimilar etanercept. One-year treatment outcomes in 2061 patients with inflammatory arthritis from the DANBIO registry. Ann Rheum Dis 2019; 78:192–200.Disclosure of Interests:None declared

Outcome of atypical haemolytic uraemic syndrome relapse after eculizumab withdrawal

Background The introduction of eculizumab has significantly improved the outcome of patients with atypical haemolytic uraemic syndrome (aHUS). Because of the risk of relapse after discontinuation, eculizumab was proposed as life-long therapy. However, data on the outcome of relapse are limited. In the Netherlands, patients with aHUS are treated with a restrictive eculizumab regime and are included in a national observational study (CUREiHUS, Dutch Trial Register NTR5988/NL5833). Methods For this interim safety analysis, we evaluated the outcome of all adult patients with a suspected relapse, defined as the need to intensify eculizumab after tapering or withdrawal of therapy. Results We describe 11 patients who received renewed eculizumab therapy because of suspected relapse. In three patients with aHUS in native kidneys, estimated glomerular filtration rate (eGFR) returned to baseline value and remained stable without overt proteinuria after follow-up. Six out of eight transplanted patients responded to eculizumab therapy with improvement in eGFR. After a median follow-up of 24.6 months, a reduction of eGFR ≥25% was observed in three of these transplanted patients, which was attributed to the aHUS relapse in only one patient. Conclusions This interim analysis suggests that re-treatment with eculizumab after relapse is safe and feasible. We will continue to use our restrictive treatment strategy.

Heart rate as a marker of relapse during withdrawal of heart failure therapy in patients with recovered dilated cardiomyopathy: an analysis from TRED-HF

Introduction In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short-term during phased withdrawal of drug therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal and provide insights into the pathophysiological drivers of relapse. Purpose To investigate the relationship between changes in heart rate (HR) and relapse amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a single arm crossover phase. HR was measured at each study visit. Mean HR and 95% confidence intervals (CI) were calculated at baseline, 45 days after baseline, 45 days prior to the end of the study or relapse and at the end of the study or relapse. Patients were stratified by treatment arm and the occurrence of the primary relapse end-point. Heart rate at follow-up was compared amongst patients who had therapy withdrawn and relapsed versus those who had therapy withdrawn and did not. ANCOVA was used to adjust for differences in HR at baseline between the two groups. Results Of 51 patients randomised, 26 were assigned to continue therapy and 25 to withdraw therapy. In the randomised and cross-over phases, 20 patients met the primary relapse end-point; one patient withdrew from the study and one patient completed follow-up in the control arm but did not enter the cross-over phase. Mean HR (standard deviation) at baseline and follow-up for (i) patients in the control arm was 69.9 (9.8) & 65.9 (9.1) respectively; (ii) for those who had therapy withdrawn and did not relapse was 64.6 (10.7) & 74.7 (10.4) respectively; and (iii) for those who had therapy withdrawn and relapsed was 68.3 (11.3) & 86.1 (11.8) respectively [all beats per minute]. The mean change in HR between the penultimate visit and the final visit for those who had therapy withdrawn and did not relapse was −2.4 (9.7) compared to 3.1 (15.5) for those who relapsed. After adjusting for differences in HR at baseline, the mean difference in HR measured at follow-up between patients who underwent therapy withdrawal and did, and did not relapse was 10.4bpm (95% CI 4.0–16.8; p=0.002) (Figure 1 & Table 1). Conclusion(s) A larger increase in HR may be a simple and effective marker of relapse for patients with recovered DCM who have insisted on a trial of therapy withdrawal. Whether HR control is crucial to the maintenance of remission amongst patients with improved cardiac function, or is simply a marker of deteriorating cardiac function, warrants further investigation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation

IgA nephropathy after pembrolizumab therapy for mesothelioma

The use of immune checkpoint inhibitors (CPIs), such as pembrolizumab, for the treatment of cancer, is now prevalent. CPIs are associated with a significant side effect profile, termed immune-related adverse events (irAEs). Renal irAEs, such as interstitial nephritis, are rare, and CPI-related glomerulonephritis even rarer. This is a case report of a 72-year-old man with mesothelioma of the left lung, whose serum creatinine rose during pembrolizumab treatment. Renal biopsy revealed IgA nephropathy. Withdrawal of therapy for 2 months saw no improvement in renal function, and following recommencement, serum creatinine fluctuated at approximately 1.4 times original baseline. This report will highlight the renal irAEs to be the aware of when starting CPIs, and the importance of early renal biopsy in management.

Combination oral contraceptives – a practice-guided overview of everyday problems and their solutions

Combination oral contraceptives (COCs) are some of the most commonly prescribed drugs for women between the ages of 15–451 and while they are accepted to be safe and highly effective, their use is often associated with a number of minor sideeffects. Considering the limited nature of this review, a detailed overview of the complete clinical profile of COCs falls beyond the current scope. Rather, we will focus on the most frequently reported side-effects of COCs that do not necessitate treatment withdrawal. Adverse effects that require immediate withdrawal of therapy are usually related to deep vein thrombosis (DVT) and other cardiovascular events, malignancies or hepatic pathology2 and would require a more in-depth review.

Dying in the Intensive Care Unit (ICU): A Retrospective Descriptive Analysis of Deaths in the ICU in a Communal Tertiary Hospital in Germany

Background. Modern intensive care methods led to an increased survival of critically ill patients over the last decades. But an unreflected application of modern intensive care measures might lead to prolonged treatment for incurable diseases, and an inadaequate or too aggressive therapy can prolong the dying process of patients. In this study, we analysed end-of-life decisions regarding withholding and withdrawal of intensive care measures in a German intensive care unit (ICU) of a communal tertiary hospital. Methods. Patient datasets of all adult patients dying in an ICU or an intermediate care unit (IMC) in a tertiary communal hospital (Klinikum Hanau, Germany) between 01.01.2011 and 31.12.2012 were analysed for withholding and withdrawal of intensive care measures. Results. During the two-year period, 1317 adult patients died in Klinikum Hanau. Of these, 489 (37%) died either in an ICU/IMC unit. The majority of those deceased patients (n = 427, 87%) was 60 years or older. In 306 (62%) of 489 patients, at least one life-sustaining measure was withheld or withdrawn. In 297 (61%) of 489 patients dying in ICU/IMC, any type of therapy was withheld, and in 139 patients (28%), any type of therapy was withdrawn. Mostly, cardiopulmonary resuscitation (n = 222), invasive (n = 121) and noninvasive (n = 40) ventilation followed by renal replacement therapy (n = 71) and catecholamine therapy (n = 66) were withheld. More invasive measures as ventilation or renal replacement therapy were withdrawn in 18 and 22 patients only. After withholding/withdrawal of therapy, most patients died within two days. More than 20% of patients dying in ICU/IMC did not have an analgesic medication. Conclusions. About one-third of patients dying in the hospital died in ICU/IMC. At least one life-sustaining therapy was limited/withdrawn in more than 60% of those patients. Withholding of a therapy was more common than active therapy withdrawal. Ventilation and renal replacement therapy were withdrawn in less than 5% of patients, respectively.

Antihypertensive Effect of Switching to a Fixed Perindopril/Amlodipine Combination in Patients Ineffectively Treated by Free Sartan-Containing Combinations. Results of the AVANGARD Study

Finding the best options for combined antihypertensive therapy is one of the main tasks to be solved for achieving target blood pressure (BP) and, accordingly, reduction of the risk of complications in patients with arterial hypertension (AH).Purpose of this study was to evaluate the effectiveness of the perindopril arginine/amlodipine fixed combination in patients with 1-2 degree hypertension not achieving BP control on previous therapy with sartan-containing free combinations.Materials and methods. In the multicenter open uncontrolled observational program AVANGARD 203 doctors in 53 cities of the Russian Federation included 658 patients who had not achieved target BP on therapy with two drugs, one of which was sartan (sartan with diuretic, calcium antagonist, β-blocker, or moxonidine in 49%, 33%, 17%, and 1% of cases, respectively). This therapy was replaced with a fixed combination of perindopril arginine/amlodipine. Duration of observation was 3 months.Results. On therapy with perindopril arginine/amlodipine, BP decreased 159.9±8.5/92.1±7.4 to 125.8±7.1/77.4±5.5 mm Hg. Target BP <140/90 mm Hg was achieved in 93.5% of patients (office measurement); target BP <135/85 mm Hg - in 83.5% of patients (home measurement). Mean 24-hour BP variability decreased from 4.4±2.9/3.0±2.0 to 3.0±2.2/2.2±1.7 mm Hg (p<0.01). Number of patients complaining of headache decreased by 2.9 times, dizziness - by 2.8 times, fatigue - by 2.3 times, irritability - by 3.0 times, sleep disturbances - by 2.3 times, dyspnea - by 3.8 times, palpitations - by 2.7 times, angina pectoris attacks - by 4.6 times. Dose of perindopril arginine/amlodipine was 10/5 mg in 36.6%, and 10/10 mg in 28.3% of cases, respectively. Number ofparticipants who dropped out ofthe study prematurely was 11 (1.6%) (1 because of adverse event). Adverse events were observed in 4 more patients (2 [0.14%] - edema of lower extremities, and 2 [0.14%] -cough), but they did not require the withdrawal of therapy.Conclusion. In case of ineffective combination therapy containing sartans, transfer of patients to a fixed combination of perindopril and amlodipine should be considered.