Treatment Interruption In Patients Research Articles

Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study

BackgroundReal-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. ObjectiveThe authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. MethodsThe authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. ResultsThe authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01‒1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29‒3.08; p = 0.002) were associated with treatment interruption. Study limitationsThe main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. ConclusionsPoor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa

Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

Consequences of Discontinuing a 4/6 Cyclin D-Dependent Kinase Inhibitor During Endocrine Treatment in Hormone-Sensitive Metastatic Breast Cancer Patients in the Context of the COVID-19 Outbreak

BackgroundThe impact of some hasty medical decision made during the first wave of the Coronavirus Disease 2019 (COVID-19) remains unknown. We have evaluated the consequences of one of these precautionary measures: the withdrawal of the cyclin D-dependent kinases 4/6 inhibitor (CDK4/6i) in patients whose metastatic disease was controlled by a combination of endocrine treatment and CDK 4/6i. MethodThis study was noninterventional, retrospective, multicentric, and included 60 patients with HR+ HER2- metastatic disease. Their disease was controlled with the combination of endocrine treatment and CDK 4/6i. The CDK 4/6i was stopped for two months during the first COVID-19 outbreak. A univariate analysis was performed to assess the risk factors associated with disease progression. ResultsDuring this therapeutic break, 22 (37 %) patients had a radiological and/or clinical disease progression. Among them, the CDK 4/6i was re-introduced to 16 patients (n = 16/22; 73 %). A new line of treatment (chemotherapy or targeted therapy) was initiated due to the rapid symptomatic tumor progression in four patients (n = 4/22; 18 %). Two patients (n = 2/22) died in visceral crisis before another anti-tumoral treatment was introduced. In univariate analysis, the presence of liver metastases increased the risk of metastatic disease progression during the withdrawal of the CDK 4/6 (OR = 6.6; 95 % CI 1.87-23.22; P= .0033). ConclusionProgression was observed in 37% of patients during the two-month treatment interruption of the CDK 4/6i. A prolonged CDK 4/6i treatment interruption in patients with clinical benefit on endocrine treatment does not seem to be a reasonable option in light of these results.

"You can't touch, you can't bond": Exploring COVID-19 pandemic impacts on rheumatoid arthritis patient goals and communication with clinicians.

"You can't touch, you can't bond": Exploring COVID-19 pandemic impacts on rheumatoid arthritis patient goals and communication with clinicians.

Treatment-Interval Changes in Serum Levels of Albumin and Histidine Correlated with Treatment Interruption in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma Completing Chemoradiotherapy under Recommended Calorie and Protein Provision.

Simple SummaryTreatment interruption during concurrent chemoradiotherapy (CCRT) jeopardizes the outcomes of patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC), which is associated with increased toxicity during CCRT. Nonetheless, we found that under the provision of recommended calories (25 kcal/kg/day) and protein (1 g/kg/day) throughout the treatment course, treatment-interval changes in serum albumin and histidine levels—not treatment toxicity—greatly contributed to the interruption of treatment in patients with LAHNSCC. We believe that serum levels of albumin and histidine should be integrated into the routine nutritional assessment of patients undergoing CCRT.We investigated risk factors for treatment interruption (TI) in patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC) following concurrent chemoradiotherapy (CCRT), under the provision of recommended calorie and protein intake; we also evaluated the associations between clinicopathological variables, calorie and protein supply, nutrition–inflammation biomarkers (NIBs), total body composition change (TBC), and a four-serum-amino-acid metabolite panel (histidine, leucine, ornithine, and phenylalanine) among these patients. Patients with LAHNSCC who completed the entire planned CCRT course and received at least 25 kcal/kg/day and 1 g of protein/kg/day during CCRT were prospectively recruited. Clinicopathological variables, anthropometric data, blood NIBs, CCRT-related factors, TBC data, and metabolite panels before and after treatment were collected; 44 patients with LAHNSCC were enrolled. Nine patients (20.4%) experienced TIs. Patients with TIs experienced greater reductions in hemoglobin, serum levels of albumin, uric acid, histidine, and appendicular skeletal mass, and suffered from more grade 3/4 toxicities than those with no TI. Neither increased daily calorie supply (≥30 kcal/kg/day) nor feeding tube placement was correlated with TI. Multivariate analysis showed that treatment-interval changes in serum albumin and histidine levels, but not treatment toxicity, were independently associated with TI. Thus, changes in serum levels of albumin and histidine over the treatment course could cause TI in patients with LAHNSCC following CCRT.

Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways.

BackgroundAcquired pemetrexed resistance leads to treatment interruption in patients with malignant pleural mesothelioma (MPM). Insulin-like growth factor-I receptor (IGF-1R) inhibitor is a candidate for treating pemetrexed-naïve MPM. However, the efficacy of cytotoxic and targeted drugs in acquired-pemetrexed resistant MPM is unclear. We explored anticancer drugs, including the IGF-1R inhibitor picropodophyllin, against acquired pemetrexed-resistant MPMs.MethodsAcquired pemetrexed-resistant human MPM cell lines, named as H2452/PEM and 211H/PEM after their parental lines H2452 and 211H, respectively, were established by exposure to pemetrexed in vitro. Picropodophyllin and siRNA for IGF-1R knockdown were used to evaluate the efficacy of IGF-1R inhibition. Immunofluorescence was used to evaluate microtubule localization. The efficacy of picropodophyllin was evaluated in 3-dimensional MPM models.ResultsThe acquired pemetrexed-resistant MPM lines retained their resistance after the removal of culture treatment. IGF-1R levels in H2452/PEM cells were higher than those in H2452 cells but not in 211H/PEM cells compared to the respective parental line. Picropodophyllin induced sub-G1 arrest in H2452/PEM cells but induced G2/M phase arrest in 211H/PEM cells, leading to caspase-independent cell death in the two acquired pemetrexed-resistant MPM lines. Although picropodophyllin inhibited phosphorylation of IGF-1R, specific inhibition of IGF-1R by RNA interference did not reduce the viability of pemetrexed-resistant MPM lines. Additionally, picropodophyllin reduced the viability of both IGF-1R knockdown pemetrexed-resistant MPM cells. Picropodophyllin was cytotoxic in acquired-pemetrexed-resistant MPM lines because of inhibition of microtubule formation and induction of aberrant mitosis. Moreover, combination treatment with picropodophyllin and vinorelbine synergistically affected the pemetrexed-resistant MPM lines but not the parental lines. Furthermore, we observed a similar efficacy of picropodophyllin in 3-dimensional pemetrexed-resistant MPM models.ConclusionsPicropodophyllin may offer novel therapeutic properties for treating acquired pemetrexed-resistant MPM. Targeting tubulin may be an important strategy in the treatment of MPM after the discontinuation of pemetrexed.

Photobiomodulation as a treatment for dermatitis caused by chemoradiotherapy for squamous cell anal carcinoma: case report and literature review

In-field dermatitis is a severe and common adverse effect of radiation therapy, that can cause significant pain and treatment interruptions in patients with squamous cell anal carcinoma (SCAC) being treated with radical chemoradiation protocols. There are no established therapies for the treatment of radiation induced dermatitis. Photobiomodulation (PBM) is an effective and low-cost treatment for radiation induced mucositis, but have recently been explored to treat in-field dermatitis. We present a case report of the successful use of PBM for the treatment of dermatitis in the anal area in a patient with SCAC treated with concomitant chemoradiation with curative intent and follow with a literature review of the recent advances and possibilities of the use of PBM as a promising strategy. PBM therapy proved to be efficient in the radiodermatitis treatment, both in relieving the symptoms and controlling dermatitis, in addition to improving the patient's quality of life.

Treatment Interruptions During Stereotactic Body Radiotherapy for Prostate Cancer.

BackgroundDuring the course of radiation treatment for prostate cancer, patients may have unintentional interruptions in their treatment course due to a wide variety of factors. Stereotactic body radiation therapy (SBRT) decreases the number of treatments compared to conventionally fractionated radiation; hence, it has the potential to decrease treatment delays and non-completion. This study sought to determine the incidence of treatment delay and characterize the etiology and length in a large cohort of men treated with SBRT for their prostate cancer.MethodsOne thousand three hundred and thirty-six patients treated with SBRT from 2008 to 2021 at the Georgetown University Hospital for prostate cancer were included in this retrospective study. A treatment delay was defined as a patient requiring longer than 14 days to complete 5 fractions of SBRT. Non-completion was defined as patients treated with less than 5 fractions. In the patients who experienced delays, chart review was performed to characterize the length and etiology of each delay. Multivariate analysis was performed via binary logistic regression modeling on PSPP.ResultsAll individuals in the cohort eventually completed the planned 5-fraction regimen. Thirty-three patients experienced a treatment delay. Median length of time to complete treatment was 11 days (range 5–155 days). In patients who experienced a delay, nearly half (45.5%) experienced only a one-day delay. The most common reason for a delay was a technical issue (48.5%), including the machine maintenance, fiducial misalignment, or inadequate pretreatment bowel preparation. Other reasons included unplanned breaks due to acute side effects (21.2%), logistical issues (18.2%), non-treatment related health issues (9.1%), and inclement weather (3.0%). There were no significant sociodemographic, oncologic, or treatment variables that predicted treatment interruption on multivariate analysis.ConclusionsThe incidence of treatment interruptions in patients undergoing SBRT for their prostate cancer was low. Most treatment delays were short.

Preferred treatment regimen of aflibercept after treatment interruption in patients with neovascular age-related macular degeneration

BACKGROUND: The efficacy of antiangiogenic therapy in neovascular age-related macular degeneration depends on adherence to the intravitreal injection regimen and regular follow-up. In 2020, the COVID-19 pandemic and associated epidemiological restrictions in ophthalmological care delivery led to a massive lack of appropriate control and management of this condition.
 AIM: To determine the preferred regimen of intravitreal anti-VEGF therapy in patients with neovascular age-related macular degeneration who experienced treatment interruption due to the COVID-19 pandemic.
 MATERIAL AND METHODS: Thirty eyes of 26 patients (20 males and 6 females, mean age 73.7 10.4 years) with neovascular age-related macular degeneration were included; all of them experienced treatment interruption due to the COVID-19 pandemic during the second year of aflibercept therapy. Re-starting therapy, all patients were divided in two groups and received treatment as per the fixed dosing (bimonthly), or as pro re nata (PRN) regimen. All patients underwent standard ophthalmological examination and optical coherence tomography before and after treatment interruption as well as six months after treatment re-start.
 RESULTS: At six months after treatment re-start, best corrected visual acuity and central retinal thickness did not show statistically significant difference similar between the fixed dosing group and that of PRN dosing regimen (p = 0.34 and p = 0.85, respectively). However, patients of the fixed dosing group received for one more injection than those of the PRN group (median value 2.0 injections, 95% confidence interval 2.0-2.4; p = 0.0001). Preservation of the disease activity according to optical coherence tomography data, in the fixed regimen group was found in 10 eyes (71.4 %) versus 9 eyes (56.2 %) in the PRN group (p = 0.63).
 CONCLUSIONS: For neovascular age-related macular degeneration patients at the second year of treatment, an adequate therapeutic strategy for re-starting anti-VEGF therapy after treatment interruption appears to be the PRN regimen. PRN regimen allows reducing one injection in comparison to fixed dosing regimen with comparable functional outcomes during first 6 month.

Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial.

IntroductionSonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months.MethodsBOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected.ResultsThe incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%).ConclusionDose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control.Trial registration: ClinicalTrials.gov identifier, NCT01327053.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00619-4.

HER2 positive breast cancer: is there a preventive role of cardioprotective drugs?

Abstract Introduction In patients with breast cancer, anti-HER2-targeted therapies (AHT) are highly associated with cardiotoxicity (CT), being the main reason for treatment interruption in patients receiving adjuvant trastuzumab. Guidelines recommend regular left ventricular ejection fraction (LVEF) assessments and CT's management with cardioprotective drugs (CPD). However, while secondary prevention has already entered clinical practice, primary prevention is still in the research domain. Our aim was to evaluate risk of CT and the role of CPD in a subset of breast cancer patients treated with AHT. Methods We retrospectively analyzed a population of breast cancer female patients treated with AHT referred to Cardio-oncology consultation at a tertiary center from January 2017 to March 2020. All patients were evaluated with echocardiogram before treatment initiation and at least at 3, 6, 9 and 12-months. CT was defined as LVEF under 50% or decline of at least 10% in LVEF during follow-up. As CPD we considered renin-angiotensin-aldosterone system inhibitors and beta-blockers. Results A total of 85 patients were included with mean age of 52.4±10.2 year-old. Concerning cardiovascular risk factors 11.8% had diabetes, 32.9% dyslipidaemia, 29.4% hypertension and 22.4% were smokers or previous smokers; most patients had a high or very-high CT risk score (98.8% with score ≥5). Besides AHT, 68.2% and 80% were also on anthracyclines and radiotherapy, respectively. Patients were followed for a median follow-up of 16 months. At baseline, mean high sensitivity troponin I was 3.9 ng/L, mean LVEF was 63.1% and mean global longitudinal strain was −19.7, with all patients having normal cardiac function. During follow-up, 15.7% developed CT with a higher prevalence in patients concomitantly on anthracyclines (19.6% vs 7.4%, p=0.151). CPD was initiated or titrated in 84.6% of patients and 30.8% needed to suspend AHT; overall 92.3% of CT patients recovered. Unlike AHT suspension, CPD initiation after CT was associated with a higher rate of cardiac function recovery (100.0% vs 50.0%, p=0.020). When comparing patients already medicated with CPD before cancer treatment (41.7%) to those naïve of CPD, the first group presented a significative lower incidence of CT [2.9% vs 25.0%, p=0.006, OR=0.09 (95% CI 0.01 – 0.72)]. When analysed all sample (with or without CT), patients already on CPD also presented a higher LVEF at 6 months follow-up (62.5% vs 59.2%, t(69)=−2.4, p=0.017 at 6 months), despite a non-significative lower LVEF at baseline (62.3% vs 63.6%, p=0.139). Medication with statins before chemotherapy didn't reduce the risk of CT. Conclusion Pre-treatment with CPD was significantly associated with a lower prevalence of CT and a higher LVEF at 6-months follow-up. CPD initiation after CT was associated with cardiac function recovery. These results highlights the importance of cardiac evaluation in HER2+ patients and strengthen the primary prevention field in these patients. Funding Acknowledgement Type of funding sources: None.

Association of fear of COVID-19 with delays in care or treatment interruptions in patients with cancer.

98 Background: Patients with cancer are at risk for severe COVID-19 and may be vulnerable to health care delays. Delays or interruptions in care may lead to adverse cancer outcomes. Little is known about the relationship between fear of COVID-19 and disruptions in cancer care delivery. Methods: This longitudinal survey was distributed to individuals with cancer who received services July 2019-April 2020 from Patient Advocate Foundation, a non-profit organization that provides case management and financial aid to patients with chronic illness. Data was collected twice - early pandemic (5/20/20-7/11/20) and later pandemic (12/3/20-12/23/20). Fear of COVID-19 was assessed with the Fear of COVID-19 Scale and dichotomized as more (≥22) vs less (< 22) fearful. Respondents reported delays in care or treatment interruptions due to the pandemic and reasons for delays or interruptions. Respondents rated concern about potential long-term health issues due to delays on a 5-point Likert-like scale. We estimated predicted percentages and 95% confidence intervals (CI) using logistic regression models to assess the association of fear of COVID-19 (more vs less fearful) with delay in care or treatment interruption (any vs none) at each time point. We adjusted models for age, sex, race/ethnicity, region, annual household income, marital status, employment status, household size, Area Deprivation Index category, Rural-Urban Commuting Code category, county-level COVID-cases per 100,000, cancer type and number of comorbidities. Results: Amongst the 1,199 early pandemic survey respondents, the majority were female (72%), had household income < $48,000 (73%), and had ≥1 comorbidity (60%). 448 of the early pandemic survey respondents also completed the later survey. 464 (39%) and 166 (37%) respondents were categorized as more fearful at the early and later time points respectively. 567 (47%) and 191 (43%) reported delays or interruptions at the early and later time points respectively. The most common reported reasons for delays or interruptions were hospital/provider restrictions (early: 27%, later: 19%) and patient choice (early: 13%, later: 15%). Among respondents with delays or interruptions at each time point, > 70% were at least moderately concerned about potential long-term health issues due to delays. In adjusted models, more fearful respondents had higher predicted percentages of delayed care or treatment interruptions compared to less fearful respondents early (more fearful: 56%, 95% CI 39%-72%; less fearful: 44%; 95% CI 28%-61%) and later (more fearful: 55%, 95% CI 35%-73%; less fearful: 38%; 95% CI 22%-57%) in the pandemic. Conclusions: Fear of COVID-19 is common among patients with cancer and is linked with delays in care and treatment interruptions. System-wide strategies are needed to address fear of COVID-19 and to ensure equitable, timely, and safe access to cancer care throughout the pandemic.

Healthcare Resource Use in Patients with Immune-Mediated Conditions Treated with Targeted Immunomodulators During COVID-19 Pandemic: A Retrospective Claims Analysis.

IntroductionThe impact of the COVID-19 pandemic on routine medical care may result in altered healthcare resource use in patients with immune-mediated conditions. The aim of this study was to determine the impact of treatment interruptions in patients with and without COVID-19 infections who were treated with targeted immunomodulators (TIMs) in the USA.MethodsData from the IBM® MarketScan® Research Databases were analyzed in patients with immune-mediated conditions from January 1, 2018, through December 31, 2020. Healthcare resource use (HCRU) including hospitalizations, emergency department (ED) visits, in-person outpatient visits, and respiratory outcomes was assessed in a cohort of patients without COVID-19 who had uninterrupted versus interrupted TIM use. The impact of treatment interruption on HCRU and respiratory outcomes was also evaluated in a cohort of patients with COVID-19. Results from adjusted logistic regression were reported as adjusted odds ratios (aORs) with 95% confidence intervals.ResultsApproximately 25% of patients in both the COVID-19 (N = 787) and non-COVID-19 cohorts (N = 77,178) experienced interruptions in TIM therapy. In the non-COVID-19 cohort, the likelihood of being hospitalized was 20% less in patients with uninterrupted versus interrupted TIM use (aOR = 0.80, 95% CI 0.71–0.90). Patients with uninterrupted TIM use had a similar likelihood of an ED visit (aOR = 0.99, 95% CI 0.91–1.08) and respiratory outcome (aOR = 0.97, 95% CI 0.71–1.31) versus patients with interrupted TIM use. The likelihood of having an in-person outpatient visit was 87% greater in patients with uninterrupted versus interrupted TIM use (aOR = 1.87, 95% CI 1.81–1.94). Similar findings were observed in the COVID-19 cohort.ConclusionThis analysis of real-world claims data showed that uninterrupted TIM use was not associated with an increased likelihood of hospitalizations, ED visits, or negative respiratory outcomes compared to interrupted TIM use among patients with immune-mediated conditions, regardless of COVID-19 diagnosis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01906-4.

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review.

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.

Efficacy and Safety of Tofacitinib Re-treatment for Ulcerative Colitis After Treatment Interruption: Results from the OCTAVE Clinical Trials.

Background and AimsTofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-treatment following treatment interruption in patients with ulcerative colitis.MethodsHere, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open.ResultsMedian time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0–179.0) and 123 [95% CI, 91.0–168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months.ConclusionsMedian time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].

Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma.

Combined axitinib and immuno-oncology (IO) therapy is approved for first-line advanced renal cell carcinoma. Overlapping toxicities represent a clinical challenge. Calculating the time to resolution (TTR) of common axitinib-related adverse events (AEs) after treatment interruption may help to identify AE etiology and determine appropriate management strategies. Data from 5 randomized or single-arm axitinib monotherapy or combination studies were analyzed. Patients with histologically confirmed clear cell advanced renal cell carcinoma were pooled into 3 cohorts based on treatment received: axitinib monotherapy, axitinib+IO, and other tyrosine kinase inhibitor (TKI). Any grade and grade ≥3 treatment-emergent diarrhea, fatigue, hypertension, nausea, and palmar-plantar erythrodysesthesia syndrome were assessed. TTR was defined as the time from treatment interruption/discontinuation to resolution. The axitinib monotherapy cohort comprised 532 patients, the axitinib+IO cohort 541 patients, and the other TKI cohort 882 patients. Median TTR for all AEs (any grade) in the axitinib monotherapy cohort ranged from 1 to 3 days, except for fatigue (8 days). For diarrhea, hypertension, nausea, and palmar-plantar erythrodysesthesia syndrome, median TTRs were longer in the axitinib+IO (4-11 days) and other TKI (7-8 days) cohorts versus the monotherapy cohort. Results were similar when only AEs of grade ≥3 were considered. The TTR of monotherapeutic axitinib-related AEs is ≤3 days, except for fatigue, and generally shorter than for other single-agent TKIs and axitinib+IO. This has important implications for identifying AE etiology with combined axitinib-IO therapy and implementation of appropriate management strategies. ClinicalTrials.org identifiers: NCT00678392, NCT00920816, NCT02493751, NCT02684006, NCT02853331.

A comparison of the MNA-SF, MUST, and NRS-2002 nutritional tools in predicting treatment incompletion of concurrent chemoradiotherapy in patients with head and neck cancer.

Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9-6.3% and 14.5-18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801-0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools. MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletionand treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

Concerns, Healthcare Use, and Treatment Interruptions in Patients With Common Autoimmune Rheumatic Diseases During the COVID-19 Pandemic.

To assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. Adults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity. Among 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users (P < 0.001). Avoidance of doctor's office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04-2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25-4.08). In the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.

Abstract 3167: Immune checkpoint inhibition re-challenge after a planned treatment interruption in patients with pancreatic adenocarcinoma with mismatch repair deficient tumors

Abstract Background: Immune checkpoint inhibitors (CPI) are used in numerous solid cancers as well as hematologic malignancies. The optimal duration of immunotherapy to maintain durable responses has not been defined, neither is the efficacy of CPI when the disease progresses during a planned treatment interruption. Pembrolizumab has been approved for all mismatch repair deficient tumors regardless of histology, based on cumulative data of five clinical trials including multiple solid tumors. Only eight patients with pancreatic cancer were included in those trials used for CPI approval in this setting. Outside of this, there is currently no role for standard of care CPI in pancreatic cancer. Methods: We screened all patients with pancreatic adenocarcinoma treated at our institution and identified two patients who had mismatch repair deficient tumors and received immune checkpoint inhibitors. Results: Two patients with metastatic pancreatic cancer were retreated with an anti- PD-1 antibody after a planned treatment interruption which, did not occur in the context of disease progression or development of immune-related adverse events. Both patients were initially treated for more than one year (17 and 22 months each) with partial response of their disease, before therapy was discontinued after at least six months of stable radiographic findings were achieved. One patient had disease progression after ten months off therapy and the other 16 months after treatment discontinuation. Both were treated with the same checkpoint inhibitor upon progression and had radiographic regression of their disease within two months after treatment initiation. Both remain on CPI with continuing radiographic and clinical response. Conclusions: CPI re-challenge may be an efficient therapy when discontinued after maximal response has been achieved. Only twelve cases have been described in the literature where patients were retreated with CPI upon progression of disease while off therapy. Our case series contributes to that body of literature and is the first to describe patients with pancreatic cancer re-challenged with CPI. Mismatch repair deficient pancreatic cancers are rare, but CPI have similar efficacy compared to other tumors with similar molecular features. Citation Format: Vaia Florou, Chris Nevala-Plagemann, Kristin Barber, Jenna Mastroianni, Courtney Christine Cavaliery, Ignacio Garrido-Laguna. Immune checkpoint inhibition re-challenge after a planned treatment interruption in patients with pancreatic adenocarcinoma with mismatch repair deficient tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3167.

SAT414 - Efficacy and safety of treatment interruption in patients with HBeAg negative chronic hepatitis B

SAT414 - Efficacy and safety of treatment interruption in patients with HBeAg negative chronic hepatitis B