Discontinuation Adverse Events Research Articles

Efficacy and safety of pharmacological treatments for autoimmune disease-associated interstitial lung disease: A systematic review and network meta-analysis

BackgroundImmunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. MethodsPubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. ResultsThe analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. ConclusionsMMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.

Impact of prior lenalidomide or proteasome inhibitor exposure on the effectiveness of ixazomib-lenalidomide-dexamethasone for relapsed/refractory multiple myeloma: A pooled analysis from the INSURE study.

To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM). INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX. Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression-free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide-naïve/exposed/refractory patients. Median DOT and PFS in PI-naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable. IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide- and/or PI-nonrefractory versus refractory patients.

The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data

IntroductionIntravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking. Materials and methodsWe combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates. ResultsAt T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS. ConclusionKET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments.

Comparative effectiveness of baricitinib and alternative biological DMARDs in a Swiss cohort study of patients with RA

ObjectivesThis observational study compares the effectiveness of baricitinib (BARI), a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), with alternative biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA), from a prospective,...

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the ‘JAK-pot’ study)

BackgroundIn a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor...

Abstract C030: HARMONi-3: A randomized, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous non-small cell lung cancer

Abstract BACKGROUND In the first-line metastatic squamous non-small cell lung cancer (NSCLC) setting, treatment with the combination of a PD-1 checkpoint inhibitor plus platinum doublet chemotherapy has become standard of care1,2. The addition of antiangiogenic agents to immunotherapy has emerged as a promising strategy for cancer treatment3,4,5. Therefore, a combined anti-angiogenesis and PD-1 blockade strategy with a bispecific PD-1 and VEGF antibody may improve clinical outcomes. Ivonescimab (SMT112/AK112) is a novel tetravalent bispecific antibody (2 binding sites for PD-1 and 2 binding sites for VEGF) with an engineered Fc-null region and a half-life of 6-7 days. In the presence of VEGF, binding affinity to PD-1 increases more than 10-fold6. Given the correlation between VEGF and PD-1 expression in the tumor microenvironment6,7,8, simultaneous blockade of these 2 targets by ivonescimab drives antitumor activity9,10. Additionally, the engineered Fc-null region and shorter half-life could potentially lead to reduced adverse events​, compared to co-administration of individual anti-PD-(L)1 and anti-VEGF agents7,8,10. At ASCO 2023, Zhang L, et al. (abstract# 9087) reported Phase 2 trial data, which included 63 first-line advanced or metastatic squamous NSCLC patients without EGFR/ALK alterations treated with ivonescimab plus paclitaxel and carboplatin. These patients had an objective response rate of 67%, a median duration of response of 15 months, 9-month overall survival (OS) estimate of 93% (median OS not reached). Furthermore, ivonescimab was well tolerated in combination with platinum doublet chemotherapy with a treatment emergent adverse event discontinuation rate of 11%. TRIAL DESIGN HARMONi-3 is a randomized, blinded, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous NSCLC. Approximately 400 patients will be randomized 1:1 to receive ivonescimab (dual blockade of PD-1/VEGF) or pembrolizumab plus carboplatin-paclitaxel/nab-paclitaxel (Q3W, 4 cycles, 21 days per cycle) followed by single-agent ivonescimab or pembrolizumab maintenance therapy for up to 2 years, or until progression, or unacceptable toxicity. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and duration of response (RECIST v1.1), as well as incidence/severity of adverse events. Key eligibility criteria include treatment naïve metastatic squamous NSCLC, ECOG PS 0 or 1 and exclusion of patients with major blood vessel invasion or encasement by cancer or intratumor cavitation. Citation Format: Jonathan Riess, Shun Lu, Jarushka Naidoo, Sara Kuruvilla, Annie Hung, Ahmed Khaled, Deborah Doroshow. HARMONi-3: A randomized, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous non-small cell lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C030.

Disease characteristics, treatments, and outcomes of patients with pulmonary arterial hypertension treated with selexipag in real-world settings from the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry)

BackgroundSelexipag is an oral prostacyclin receptor agonist, indicated for pulmonary arterial hypertension to delay disease progression and reduce the risk of pulmonary arterial hypertension-related hospitalization. SelexiPag: tHe usErs dRug rEgistry (NCT03278002) was a US-based, prospective, real-world registry of selexipag-treated patients. MethodsAdults with pulmonary hypertension (enrolled 2016-2020) prescribed selexipag were followed for ≤18 months, with data collected at routine clinic visits. Patients were defined as newly or previously initiated if they had started selexipag ≤60 days or >60 days, respectively, before enrollment. ResultsThe registry included 829 patients (430 newly initiated, 399 previously initiated; 759 with pulmonary arterial hypertension), of whom 55.6% were World Health Organization functional class (FC) III/IV; 57.3% were intermediate or high risk per REVEAL 2.0. In patients with pulmonary arterial hypertension, 18-month discontinuation rates for adverse events were 22.0%, 32.0%, and 11.9%, and 18-month survival rates were 89.4%, 84.2%, and 94.5% in the overall, newly, and previously initiated patient populations, respectively. From baseline to Month 18, most patients had stable or improved FC and stable or improved REVEAL 2.0 risk category status. Discontinuation for adverse events, hospitalization, and survival were similar regardless of patients' individually tolerated selexipag maintenance dose. No new safety signals were identified. ConclusionsIn this real-world analysis of patients initiating selexipag, most patients had stable or improved FC and REVEAL 2.0 risk category. Similar to the GRIPHON trial, outcomes with selexipag in this real-world study were comparable across maintenance dose strata, with no new safety signals.

The efficacy, safety, and tolerability of an estrogen-free oral contraceptive drospirenone 4 mg (24/4-day regimen) in obese users

ObjectivesThis study aimed to compare contraceptive efficacy and safety of drospirenone 4 mg in a 24/4-day regimen in nonobese and obese users and describe pharmacokinetics according to bodyweight. Study designWe analyzed data from three drospirenone 4 mg trials (2 European and 1 United States) to report outcomes in nonobese (body mass index <30 kg/m2) and obese (body mass index ≥30 kg/m2) users. We used data from the US trial to calculate the Pearl Index (pregnancies per 100 woman-years) in nonbreastfeeding participants aged ≤35 years at enrollment for confirmed pregnancies. We assessed safety outcomes from all trials based on reported treatment-emergent adverse events. We evaluated pharmacokinetics by bodyweight in the US trial. ResultsThe three trials combined comprised 2152 nonobese and 425 obese participants, including 590 nonobese and 325 obese participants in the US trial. Eight nonobese and four obese participants had confirmed pregnancies in the US trial, resulting in Pearl Indices of 3.0 (95% CI: 1.3–5.8) and 2.9 (95% CI: 0.8–7.3), respectively. Two-hundred forty-four (11.3%) nonobese and 39 (9.2%) obese participants discontinued due to a treatment-emergent adverse event. The pharmacokinetic analysis included 814 participants with a median weight of 73 (interquartile range 61–89) kg and median plasma drospirenone exposure (AUC0–24ss) of 661.3 (interquartile range 522–828) ng∙h/mL. Changing bodyweight from the median to the fifth percentile (51 kg) or 95th percentile (118 kg) changed drospirenone exposure (AUC0–24,ss) by 22.2% and –23.6%, respectively. ConclusionsDrospirenone 4 mg demonstrated similar contraceptive efficacy for both nonobese and obese users despite a difference in exposure based on bodyweight. ImplicationsOur limited comparison between obese and nonobese users of drospirenone-only oral contraception demonstrated no evidence that efficacy or discontinuation for adverse events differs between groups. Serum drospirenone levels vary by bodyweight and may correlate with bleeding outcomes.

A Bayesian network meta-analysis of ALK inhibitor treatments in patients with ALK-positive non-small cell lung cancer.

To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK-positive non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK-positive NSCLC. The effectiveness of ALKis was evaluated by assessing progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety. We conducted an indirect treatment comparison between all ALKis by using a Bayesian model. Twelve eligible trials including seven treatments were identified. All of the ALKis improved PFS and ORR relative to chemotherapy. Consistent with alectinib, brigatinib, lorlatinib, and ensartinib showed significant differences versus crizotinib and ceritinib. Lorlatinib seemed to prolong PFS compared with alectinib (0.64, 0.37 to 1.07), brigatinib (0.56, 0.3 to 1.05), and ensartinib (0.53, 0.28 to 1.02). No significant difference was found among them in OS except for alectinib versus crizotinib. Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR. Subgroup analyses based on BM indicated that PFS was dramatically lengthened by lorlatinib. Compared with other ALKis, alectinib notably reduced the rate of SAEs. There was no striking difference between discontinuation for AEs, except for ceritinib versus crizotinib. The ranking of validity showed that lorlatinib had the longest PFS (98.32%) and PFS with BM (85.84%) and the highest ORR (77.01%). The rank of probabilities showed that alectinib had the potentially best safety in terms of SAEs (97.85%), and ceritinib had less discontinuation (95.45%). Alectinib was the first choice for patients with ALK-positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long-term follow-up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors. Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630nm wavelength) was applied at 200J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study). There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%. PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.

MP11-15 THE EFFECT OF A REDUCED DOSE OF APALUTAMIDE ON SKIN-RELATED ADVERSE EVENTS IN ADVANCED PROSTATE CANCER: A MULTICENTER RETROSPECTIVE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP11-15 THE EFFECT OF A REDUCED DOSE OF APALUTAMIDE ON SKIN-RELATED ADVERSE EVENTS IN ADVANCED PROSTATE CANCER: A MULTICENTER RETROSPECTIVE STUDY Kyo Togashi, Mutsu, Japan Shingo Hatakeyama, Ryuji Tabata, Daiji Fujimori, Yohei Kawashima, Toshikazu Tanaka, Teppei Okamoto, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto Hashimoto, Satoshi Sato, and Chikara Ohyama Kyo TogashiKyo Togashi More articles by this author , Mutsu, Japan Shingo HatakeyamaMutsu, Japan Shingo Hatakeyama More articles by this author , Ryuji TabataRyuji Tabata More articles by this author , Daiji FujimoriDaiji Fujimori More articles by this author , Yohei KawashimaYohei Kawashima More articles by this author , Toshikazu TanakaToshikazu Tanaka More articles by this author , Teppei OkamotoTeppei Okamoto More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro Hashimoto HashimotoYasuhiro Hashimoto Hashimoto More articles by this author , Satoshi SatoSatoshi Sato More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to evaluate the effect of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 treatment-naïve metastatic castration-sensitive PC (mCSPC) patients treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin AEs in patients with small body size, post-skin AE discontinuation rate, and the effect of apalutamide dose reduction on CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin AE rate was not significantly different between the groups (55% vs. 43%, p=0.761). The incidence rate of skin AEs in the reduced dose of apalutamide was significantly lower in patients with small body size (body weight <67 kg and body mass index <24 kg/m2) than in those with other body sizes. The apalutamide discontinuation rate after skin AEs significantly differed between the full dose (50%) and reduced dose (16.7%) groups. Of the 72 patients with mCSPC, the CRPC-free survival was not significantly different between the full dose and reduced dose groups. CONCLUSIONS: Apalutamide dose reduction was not significantly associated with the incidence of skin AEs. However, dose reduction for patients with small body size may alleviate skin AEs without sacrificing oncological outcome. Source of Funding: nothing © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e130 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyo Togashi More articles by this author Mutsu, Japan Shingo Hatakeyama More articles by this author Ryuji Tabata More articles by this author Daiji Fujimori More articles by this author Yohei Kawashima More articles by this author Toshikazu Tanaka More articles by this author Teppei Okamoto More articles by this author Hayato Yamamoto More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto Hashimoto More articles by this author Satoshi Sato More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF downloadLoading ...

Intermittent Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment Maintains High Level of Viral Suppression in Virally Suppressed People Living with HIV.

In this observational study, we aimed to evaluate whether bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered 5 or 4 days a week is able to maintain viral suppression in people living with HIV (PLHIV). We enrolled 85 patients who initiated intermittent B/F/TAF between 28 November 2018 and 30 July 2020: median (IQR) age 52 years (46-59), duration of virological suppression 9 years (3-13), CD4 633/mm3 (461-781). Median follow-up was 101 weeks (82-111). The virological success rate (no virological failure [VF]: confirmed plasma viral load [pVL] ≥ 50 copies/mL, or single pVL ≥ 200 copies/mL, or ≥50 copies/mL with ART change) was 100% (95%CI 95.8-100) and the strategy success rate (pVL < 50 copies/mL with no ART regimen change) was 92.9% (95%CI 85.3-97.4) at W48. Two VF occurred at W49 and W70, in 2 patients self-reporting poor compliance. No resistance mutation emerged at time of VF. Eight patients presented strategy discontinuation for adverse events. There was no significant change in the CD4 count, residual viraemia rate, neither body weight during follow-up, but a slight increase in CD4/CD8 ratio (p = 0.02). In conclusion, our findings suggest that B/F/TAF administered 5 or 4 days a week could maintain the control of HIV replication in virologically suppressed PLHIV while reducing cumulative exposition of ART.

Telephone follow-up contributes to improving adherence and treatment duration in patients with hepatocellular carcinoma treated with lenvatinib.

This study aimed to investigate whether telephone follow-up by clinical pharmacists for unresectable hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN) contributes to improved adherence and treatment duration for LEN. This retrospective study enrolled 132 patients with HCC who were treated with LEN. The patients were classified into non-telephone follow-up (n=32) or telephone follow-up groups (n=100) [the latter group was further classified into family-pharmacist (FP) telephone follow-up (n=18), or hospital family-pharmacist (HFP) telephone follow-up (n=82) groups]. The progression-free survival (PFS) in the telephone follow-up group was significantly higher than that in the non-telephone follow-up group (PFS 6.1months vs 3.7months, P=0.001, respectively). Although treatment duration was significantly longer in the telephone follow-up group than in the non-telephone follow-up group [median treatment duration: 10.4months vs 4.1months, P=0.001, respectively.], no significant differences were noted between the HFP telephone follow-up group and FP telephone follow-up groups (10.3months vs 13.3months, P=0.543). Self-interruption and adverse-event discontinuation in the HFP-telephone follow-up group were significantly lower than those in the FP-telephone and non-telephone groups (0% vs 11.1% vs 18.8%; P<0.001, 25.6% vs 33.3% vs 53.1%; P=0.022, respectively). Telephone follow-up contributes to prolonged treatment duration for LEN in patients with HCC treated. Moreover, telephone follow-up with an HFP may further improve treatment adherence.

The effect of reduced dose of apalutamide on skin adverse events in advanced prostate cancer: A multicenter retrospective study.

151 Background: We aimed to evaluate the effect of a reduced dose of apalutamide on skin-related adverse events (AEs) and castration-sensitive prostate cancer (CRPC)-free survival in patients with advanced prostate cancer. Methods: We retrospectively evaluated 35 patients with non-metastatic CRPC and 72 treatment naïve metastatic castration-sensitive prostate cancer (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose-reduction on skin AEs. The secondary outcomes included the effect of apalutamide dose-reduction on skin AE in patents with small body size, post-skin AEs discontinuation rate, and the effect of apalutamide dose-reduction on CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. Results: Of 107 patients, 65 (60.7%) and 42 (39.3%) patients were treated with full- and reduced-dose of apalutamide, respectively. The skin AEs rate was not significantly different between the groups (55% vs. 43%, P = 0.761). The incident of skin AEs in the reduced dose of apalutamide were significantly lower in patients with small body size (body weight &lt;67kg and body mass index &lt; 24kg/m2) than those in other body sizes. Apalutamide discontinuation rate after skin AEs was significantly different between the full-dose (50%) and reduced-dose (16.7%) groups. Of 72 patients with mCSPC, the CRPC-free survival was not significantly different between the full- and reduced-dose groups. Conclusions: A reduced dose of apalutamide was not significantly associated with the incident of skin AEs. However, dose reduction for patients with small body size may decrease skin AEs without sacrificing oncological outcome.

Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa.

Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Among 242 patients, 131 (54%) were male, 97 (40%) were living with HIV, 175 (72%) received second-line treatment prior to first hospitalization, and 191 (79%) died during the study period. At initial hospitalization, 134 (55%) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42%) had resistance to ofloxacin and/or amikacin. Most patients (129 [53%]) had multiple hospitalizations and DST changes occurred in 146 (60%) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18%), capreomycin (18%), PAS (17%) and kanamycin (16%) than other DR-TB drugs (P<0.001), including ethionamide (8%), moxifloxacin (7%), terizidone (7%), ethambutol (7%), and pyrazinamide (6%). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56-1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51-0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.

P771 Biologics versus azathioprine in steroid-dependent ulcerative colitis: results from the A.U.R.O.R.A. database

Abstract Background The A.U.R.O.R.A. database is an Italian multicenter retrospective cohort of patients with ulcerative colitis (UC) treated with the first biological drugs (infliximab biosimilar- IFX-B, adalimumab-ADA, golimumab-GOL, vedolizumab-VDZ) approved in Italy after patent expire of IFX-originator. In a previous published study,1 we showed similar efficacy among all drugs according to the rigorous outcome of 1-year “continuous clinical remission” (CCR). In this study, we focused only on steroid-dependent UC, by comparing all drugs to each other and to patients treated with steroids followed by azatioprine (AZA) monotherapy. Methods All consecutive patients with steroid-dependent UC, treated with IFX-B, ADA, GOL or VDZ after their approval in 2014-2019, were followed-up for 1 year or until drug discontinuation for relapse or adverse events. All drugs were compared to each other and to steroid-dependent patients treated with steroids + AZA in 2006-2014. A propensity score analysis was performed to balance differences at baseline. The primary endpoint was the 1-year CCR, defined as steroid-free clinical remission with Mayo partial score ≤2 (with no bleeding), without any clinical relapse or treatment optimization after the first remission was achieved, and without drug withdrawal due to adverse events. Treatment optimization was defined as the addition of systemic/topical steroids, oral/topical mesalazine or any dose escalation of biologics Results 370 patients (IFX-B=62, ADA=68, GOL=56, VDZ=100, AZA 84) with steroid-dependent UC were included. No significant differences were found among each biological drug according to the 1-year CCR primary end-point (34%, 29%, 30%, 39%, respectively). In patients naive to immunesuppressors and biologics (n= 17, 25, 24 10, 79, respectively), AZA showed significantly higher rate of CCR (68%) than each biological drug (35%, 44%, 33%, 60%; p=0.000 for each comparison) or all biologics as a whole (41%; p=0.012). Adverse events occurred significantly less frequently with ADA (8%) than IFX (29%), GOL (20%) and AZA (26%) in the overall population, but were similar across all drugs in the naive population. Discontinuation for adverse events occurred more frequently (p&amp;lt;0.05) with both IFX-B (16%) and AZA (14%) than ADA (3%), GOL (4%), and VDZ (1%) in the overall population, but not in the naive population (18%, 15%, 4%, 4%, 0%, respectively). Conclusion In steroid-dependent UC, anti-TNF-alpha agents and VDZ were equally effective at 1 year according to the concept of CCR. AZA still appears an effective first-line strategy in the biological era. 1Cassinotti A. et al. Eur J Gastroenterol Hepatol. 2022;34:1238-46. Guided Poster Session

1006. High Adherence and Cost Savings with Home OPAT Provided through Infectious Disease Physician Office Infusion Centers

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to be safe and effective for self-administration but can lead to non-adherence without supervision. A physician office infusion center (POIC) with pharmacy services provides a unique opportunity to impact adherence and OPAT management. Patients (pts) typically come to the POIC weekly for catheter care, laboratory collection, medication pick-up and as needed provider visits. Often, close provider oversight allows for de-escalation of OPAT. We evaluated adherence to therapy, visits and associated cost saving in pts receiving self-administered OPAT through POICs. Methods Pts receiving home OPAT in 2021 were randomly selected from participating sites based on annual pt volume. Adherence was assessed as % of OPAT doses dispensed vs. doses missed. Frequency of office visits for routine catheter care and labs along with OPAT completion were collected. Cost savings were calculated in days of OPAT saved due to therapy de-escalation and response to therapy, based upon published daily costs of OPAT. Pt characteristics, OPAT duration, infection type and regimen were captured. Results A total of 125 of 2180 pts from 13 POICs nationally were included (mean age 50±18 years, 52% male). Mean OPAT duration was 38±9 days. Predominant infections were bone and joint (38%), complicated skin (18%), intra-abdominal (15%) and bacteremia (14%). The most common antimicrobials were cephalosporins (54%) with 20 pts self-administering ≥2 drugs. Pts had a mean of 6±3 POIC visits during the therapy course with completion as scheduled in 703/706 visits (99.6%). OPAT was completed as planned in 118 pts (94%), with discontinuations for adverse events (n=3), hospitalization (n=2), or non-adherence (n=2). Overall adherence rate was 99.3% with 51 missed of 7315 doses dispensed. De-escalation during OPAT saved 533 doses equating to 307 days of OPAT (2.4 days/pt). Based on an average daily OPAT cost of $140, this saved $42,980 in the randomized cohort and an estimated $749,571 annually in the entire population. Conclusion Home OPAT through an ID POIC was associated with a very high rate of adherence and compliance to scheduled visits in pts. ID oversight resulted in healthcare cost savings through onsite antimicrobial stewardship and therapy management. Disclosures Lucinda J. Van Anglen, PharmD, Merck &amp; Co.: Grant/Research Support|Paratek: Grant/Research Support.

Brief Report: Efficacy and Safety of Efavirenz, Raltegravir, and Dolutegravir in HIV-1/TB Coinfection. A Multicenter Retrospective Cohort Study in France.

There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) coinfected patients. We conducted a 10-year retrospective study in 4 centers in France. We included all HIV-1/tuberculosis coinfected patients starting antiretroviral therapy with a rifampicin-based regimen, with a plasma HIV RNA level (VL) > 1000 copies/mL. The primary endpoint was the proportion of patients with virological success that is, with VL <50 copies/mL at W48 using an Intention-To-Treat analysis, using last-observation-carried-forward to impute missing data. We also assessed antiretroviral therapy safety, analyzing treatment discontinuation for adverse events. Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and 2 NRTIs) and 59 (50.4%) with efavirenz (and 2 NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an Intention-To-Treat analysis ( P = 0.68). Emergence of drug resistance in patients with virological failure, defined as a VL >50 copies/mL, was observed in 3 patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively ( P = 0.67). In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB coinfected patients.

P188 Baricitinib effectiveness after a previous inadequate response to an alternative JAK inhibitor: results from the Swiss rheumatoid arthritis register

Abstract Background/Aims Previous research has suggested that switching between b/tsDMARDs with different mode of action may be more effective than switching agents within the same mechanism of action. Limited data exists about the impact of an inadequate response to a previous JAK-inhibitor (JAKi) on subsequent JAKi effectiveness. Methods This is a nested study within the Swiss Clinical Quality Management (SCQM) registry of RA patients. All patients initiating baricitinib treatment courses (BARI) between 01-09-2017 and 01-06-2020, with at least one follow-up visit, were included. We compared the time to treatment discontinuation, as a measure of drug effectiveness, of BARI with a previous history of an inadequate response (IR) to tofacitinib (“BARI-post-TOFA”) or without (“BARI-initial”). Tofacitinib IR was defined as previous tofacitinib treatment discontinuation for adverse events or for ineffectiveness. Baseline characteristics were compared using t-tests or χ2. We used Kaplan-Meier curve to display crude time to discontinuation and a Cox model to estimate adjusted hazard ratio (HR). Cox model was adjusted for potential confounding factors: age, BMI, concomitant csDMARD, concomitant steroid usage, baseline CDAI, disease duration, smoking status, line of therapy, gender and seropositivity to RF/ACPA. Results Of the 273 included BARI, 72 were initiated in patients with a history of a previous tofacitinib IR (Table 1). No differences were found between the “BARI-post-TOFA” and the “BARI-initial” groups in terms of time-to-discontinuation, as demonstrated by both the unadjusted Kaplan-Meier survival analysis (Log-rank p = 0.44) and the fully adjusted Cox analysis (Hazard Ratio BARI-post-TOFA vs BARI-initial = 0.76 (95% IC [0.42 - 1.34]; p = 0.34). Other covariates significantly associated with drug maintenance were active smoking (p = 0.03) and CDAI score (p &amp;lt; 0.01). Conclusion In this preliminary analysis, a history of prior tofacitinib IR did not appear to significantly impact subsequent drug maintenance of baricitinib. Disclosure B.T.P. Gilbert: Other; Invited speaker for Lilly Symposium SGR Congress Lausanne (2021). D.S. Courvoisier: None. D. Mongin: None. K. Lauper: None. V.A. Guimaraes: Other; Clinical Research Scientist Immunology at Eli Lilly (Suisse) S.A. R.B. Mueller: None. A. Finckh: Grants/research support; Invited speaker and consultant for Eli Lilly. Has received research grant from Eli Lilly.

OAB-003: CARDAMON:Carfilzomib (K) maintenance following Autologous Stem Cell Transplant (ASCT) or carfilzomib-cyclophosphamide-dexamethasone (KCd) consolidation for newly diagnosed (NDTE) multiple myeloma (MM)

<h3>Background</h3> The role of upfront ASCT for NDTE MM remains under evaluation with high MRD rates following novel induction and consolidation (cons) strategies. K maintenance represents an alternative strategy to lenalidomide maintenance. The CARDAMON trial investigated K maintenance following KCd induction plus either ASCT or KCd cons. <h3>Methods</h3> NDTE pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons followed by 18 cycles K maintenance (56mg/m² D1,8,15). Flow cytometric MRD (10-5) was assessed post induction, pre-maintenance and at 6 months maintenance. Primary endpoints were ≥VGPR post induction and 2-year PFS from randomisation. Secondary endpoints included improvements in disease response and MRD conversion following ASCT/ cons and maintenance. <h3>Results</h3> 281 patients were registered, with 218 randomised to either ASCT or cons. The median PFS for ASCT was not yet reached vs 3.4 years for cons, with cons failing to show non-inferiority (difference in 2-year PFS 6.5%, 70% CI 1.0% to 11.1%). 196 patients received K maintenance (99 ASCT, 97 cons), 17 remain on treatment. A median of 16 cycles (1-18) were given over a median of 15.9 months (0-21.5). COVID-19 led to maintenance treatment interruptions in 41 (8 ASCT, 6 Cons) and treatment discontinuation in 15 (9 ASCT, 6 Cons). The median K dose given was 50.6mg/m2 and was similar across both arms (51.2 vs 49.4mg/m2, p=0.03). K maintenance was discontinued for PD in 14.1% (ASCT) vs 22.7% (cons), and for adverse events (AEs) in 7.1% (ASCT) vs 4.1% (cons). Most common AEs were hypertension and infections and more ≥G3 AEs were noted in ASCT vs cons (p=0.01). Patient/ clinician withdrawals from maintenance were low but occurred more in the ASCT arm (9.1% vs 1%). MRD neg patients post ASCT/ Cons had a longer PFS than MRD pos (p=0.002); with a higher MRD neg rate in the ASCT arm (53.6% vs 35.1% in Cons, p=0.01). MRD neg patients at 6 months post maintenance also had longer PFS (p=0.004 cf MRD pos patients); again with higher MRD neg rates in the ASCT arm (58.1% ASCT vs 40.5% Cons, p=0.02). There was no difference in PFS for MRD neg patients according to treatment arm from PBSCH, post-ASCT/ Cons or 6 months maintenance timepoints. Overall, 27.8% of MRD pos patients converted to MRD neg post ASCT/ Cons with more converting with ASCT (39.1% ASCT vs 16.1%, p=0.004). 23.5% of MRD pos patients converted to neg during maintenance (30.6% ASCT, 17.8%: p=0.2). Maintenance of MRD negativity over the first 6 months was similar between ASCT and Cons arms (p=0.3). There was no evidence that the timing of achievement of MRD negativity impacted PFS. <h3>Conclusions</h3> K maintenance at 56mg/m2 weekly was deliverable and tolerable, with continued higher MRD neg rates at 6 months post-ASCT compared to post-Cons. However more ≥G3 AEs and discontinuations for AEs/ patient choice were noted for K maintenance after ASCT.