Long-term Maintenance Therapy Research Articles

POSC122 Cost-Effectiveness of ALPHA-2 Adrenergic Agonist (LOFEXIDINE) and Long-Acting Injectables for Treatment of Opioid Use Disorder

Lofexidine (the first US-approved non-opioid medication for opioid withdrawal management) and novel pharmaceutical formulations, extended-release naltrexone and extended-release buprenorphine depot injection for long-term maintenance therapy, are available alongside the traditional opioid agonists to treat opioid use disorder (OUD), albeit the higher costs. This study evaluates the incremental cost-effectiveness of these newer pharmacotherapies from the US healthcare perspective.

Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis.

Vulvovaginal candidiasis is a common infection associated most often with the overgrowth of the fungal species Candida albicans. Although most women will have at least one episode of vulvovaginal candidiasis in their lifetime, some will experience recurrent infections. Recurrent vulvovaginal candidiasis can significantly impact quality of life, causing both physical and psychological symptoms, and poses a substantial financial burden for women and the health care system. Acute vulvovaginal candidiasis infections are often diagnosed symptomatically by clinicians or self-diagnosed by patients themselves; this can result in over- and underdiagnosis, as well as misdiagnosis, and has the potential to lead to ineffective treatment and incomplete infection resolution. Clinical diagnosis should include confirmatory laboratory tests, including microscopy and fungal culture, especially in women with a history of recurrent vulvovaginal candidiasis, who are more likely than women with vulvovaginal candidiasis to be infected with less-common Candida species or with azole-resistant strains. With proper diagnosis, most acute vulvovaginal candidiasis episodes can be successfully treated; however, women with recurrent vulvovaginal candidiasis may require long-term maintenance therapy. US-based guidelines recommend ⩽6 months of maintenance fluconazole treatment, but infection recurs in up to 50% of women treated. There are currently no US Food and Drug Administration–approved treatments for recurrent vulvovaginal candidiasis; however, several promising treatments for recurrent vulvovaginal candidiasis are in development.

The role of cytomegalovirus colitis on short- and long-term outcomes for patients with ulcerative colitis

Background and Aim Cytomegalovirus (CMV) colitis brings great obstacles for treatment of ulcerative colitis (UC). We aimed to assess the impact of CMV colitis on prognostic outcomes and associated risk factors for UC patients. Methods A consecutive 77 inpatients diagnosed as UC were collected retrospectively from January 2012 to December 2015. About 33 patients were defined with CMV colitis by histological tests of colon mucosa. Clinical characteristics and outcomes were compared between patients with CMV colitis or those without. The primary outcomes were UC-related colectomy or the first time of disease relapse after discharge. Results 33 CMV colitis patients had higher frequency of recent steroid treatment (81.8% vs. 31.8%, p < .001), older age of onset (45.3 ± 13.0 vs. 44.5 ± 15.7 years, p = .028) and more severe colitis (p < .001) characterized by lower hemoglobin (99.0 ± 23.2 vs. 114.6 ± 22.6 g/L, p = .004), albumin (29.7 ± 4.6 vs. 35.4 ± 6.5 g/L, p < .001), immunoglobulin G [8.8 (5.9–10.6) vs. 12.3 (9.3–16.2) g/L, p = .003] and higher C reactive protein [48.5 (21.6–73.8) vs. 9.1 (3.6–35.0) mg/L, p < .001]. The occurrence of UC-related colectomy in patients with CMV colitis was more frequent (48.5% vs 20.5%, p<.01) and CMV colitis was proved to be one of risk factors of colectomy with a hazard ratio of 3.15 (95%CI 1.387–7.171, p = .006), mainly in a short term period. UC-related complications almost occurred within 1 year since CMV colitis diagnosis. And UC patients with CMV colitis always experienced early relapse. Conclusions CMV colitis increases the colectomy risk mainly in a short term due to severe inflammatory response, early-onset complications or medication treatment failure. There is also potential correlation between CMV colitis and early relapse. Short-term therapy for UC patients with CMV colitis should be more concerned on controlling systemic inflammation and reducing complications whereas long-term maintenance therapy may not require more aggressive intervention.

Efficacy and Safety of Different Formulations of Calcipotriol/Betamethasone Dipropionate in Psoriasis: Gel, Foam, and Ointment

Preparations containing calcipotriol combined with betamethasone dipropionate (in the forms of ointment, gel, and foam) are available for the topical treatment of psoriasis. This review summarizes the differences in the efficacy and safety of these formulations, as well as the preferences of patients with various forms of psoriasis (plaque, scalp, and nail psoriasis). It has been documented that foams provide higher bioavailability, resulting in increased efficacy in plaque psoriasis compared to ointments and gels. Gels or foams are preferred by patients for their different practical qualities (e.g., gels for “easy application”, and foams for “immediate relief”). The available data indicate that ointments may be the most effective formulation in nail psoriasis, and gels are preferred by patients with scalp psoriasis because of their cosmetic features. Treatment with a foam formulation is associated with a lower number of medical appointments compared to treatment with an ointment and with a lower probability of developing indications for systemic treatment. The safety profiles of foams, ointments, and gels are comparable, with the most common adverse effect being pruritus at the application site (in 5.8% of the patients). A long-term proactive maintenance therapy markedly reduces the number of relapses and is likely to close the gap between topical and systemic treatment in psoriasis.

Substantiation of Using Pimecrolimus 1% Cream in Proactive Therapy of Children with Atopic Dermatitis

Atopic dermatitis (AtD) is multifactorial inflammatory skin disease with high prevalence in pediatric population. It is crucial to implement long-term maintenance therapy to prevent AtD exacerbations according to current clinical guidelines and expert reports. The article summarizes the results of the major studies on using pimecrolimus 1% cream. Its efficacy and safety in long-term proactive therapy of children with AtD are presented.

RADICAL TREATMENT FOR BLASTOMYCOSIS FOLLOWING FAILED LIPOSOMAL AMPHOTERICIN

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary blastomycosis is a respiratory disease that is caused by the fungus Blastomyces, most commonly through inhalation of the fungal spores. Infected individuals typically show symptoms 3 weeks to 3 months after inhalation of these spores. About 50% of patients with pulmonary blastomycosis are asymptomatic. Individuals with severe blastomycosis are initially treated with intravenous antifungal therapy with Amphotericin followed by long-term itraconazole maintenance therapy. CASE PRESENTATION: We present the case of an immunocompetent young male who was diagnosed with pulmonary Blastomyces dermatitidis and had poor clinical response to 10 days of liposomal Amphotericin B (L-AmB). Due to persistent hypoxia and hypoxemia, the patient was endotracheally intubated and extracorporeal membrane oxygenation (ECMO) was initiated. Due to the poor response to L-AmB, L-AmB was discontinued in favor of continuous infusion of amphotericin B deoxycholate (AmB-d). Additionally, the patient was started on a short course of corticosteroids. With the combination of these treatments, the patient had significant clinical improvement. The patient was taken off ECMO on day 9 and extubated on day 12 after the initiation of AmB-d. DISCUSSION: Literature review yielded limited information regarding treating blastomycosis with a continuous AmB-d infusion. To our knowledge, this is the third case reported in the literature of the use of continuous AmB-d infusion for the treatment of severe blastomycosis. ARDS due to blastomycosis has a mortality of up to 80% with the standard of treatment in such severe cases being liposomal amphotericin. Given that ECMO and AmB-d infusion were started concurrently, it is unclear if the significant improvement was due to the decrease in burden on the respiratory system by ECMO or due to AmB-d infusion demonstrating higher effectiveness compared to liposomal amphotericin B, or a combination of both. A case reported by Branick, K et al. discusses a patient on ECMO treated with L-AmB without improvement until AmB-d continuous infusion was started. Even though they attributed the treatment failure to clogging of the ECMO circuit by L-AmB, their belief was that ECMO is not an effective means to treat Blastomycosis and therefore, believed that the patient improvement was solely due to AmB-d infusion. CONCLUSIONS: While L-AmB is considered first line treatment for blastomycosis, the mortality remains high in those with ARDS associated with blastomycosis. This case demonstrates the importance of considering AmB-d in patients with severe blastomycosis who may have poor response to L-AmB. ECMO and steroids were also included in the patient's treatment plan which may have contributed to the patient's improvement. In a disease process with such high mortality rates, the need for continued evaluation of treatment options is crucial given the limited treatment options currently available. REFERENCE #1: Branick K, Taylor MJ, Trump MW, Wall GC. Apparent interference with extracorporeal membrane oxygenation by liposomal amphotericin B in a patient with disseminated blastomycosis receiving continuous renal replacement therapy. Am J Health Syst Pharm. 2019;76(11):810-813. REFERENCE #2: Meyer KC, McManus EJ, Maki DG. Overwhelming pulmonary blastomycosis associated with the adult respiratory distress syndrome. N Engl J Med. 1993;329(17):1231-1236. REFERENCE #3: Lahm T, Neese S, Thornburg AT, Ober MD, Sarosi GA, Hage CA. Corticosteroids for blastomycosis-induced ARDS: a report of two patients and review of the literature. Chest. 2008;133(6):1478-1480. DISCLOSURES: No relevant relationships by Christopher Chew, source=Web Response No relevant relationships by Henry Ogbuagu, source=Web Response No relevant relationships by Dhaval Patel, source=Web Response No relevant relationships by Nikhilesh Thapa, source=Web Response No relevant relationships by Merin Varghese, source=Web Response

The Use of Sunitinib as Maintenance Therapy in a Pediatric Patient With a Poorly Differentiated Thymic Carcinoma.

Thymic carcinomas are rare aggressive mediastinal tumors with a median survival of 2 years. We present a pediatric patient who was diagnosed with metastatic thymic carcinoma and showed continuous improvement of his primary mass and lung metastases with a regimen of cisplatin/docetaxel followed by long-term maintenance therapy with sunitinib for over 5 years. This report demonstrates a long-term positive treatment effect using chemotherapy followed by sunitinib in an advanced thymic carcinoma. We are not aware of other reports of pediatric patients with metastatic thymic carcinoma treated with sunitinib maintenance who maintained a durable response for this prolonged period of time.

Combination chemoradiotherapy with temozolomide, vincristine, and interferon-\u03b2 might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma

BackgroundThis investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-β for glioblastoma.MethodsThe initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-β. Maintenance chemotherapy comprised monthly TMZ, continued for 24–50 cycles, plus weekly IFN-β continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status.ResultsForty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5–55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9–34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%.ConclusionsThe 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-β tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor.Trial registrationUniversity Hospital Medical Information Network (number UMIN000040599).

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study

BackgroundFecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).MethodsSubjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.ResultsTwelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.ConclusionThese pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.

Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease.

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.

Emerging Clinical Concepts for Personalized Therapy in Multiple Myeloma; Systemtic Review

Introduction:Personalization of Multiple Myeloma (MM) therapy according to individual patient requirements is an emerging need. Most patients with newly diagnosed MM are age 65 years or above and may have unique challenges due to comorbidities and risks for toxicity. Diverse prognostic factors, cytogenetic aberrations, age associated comorbidities, disease stage and systemic complications of MM call for tailoring the therapeutic regimens for MM according to each patient's unique presentation. Bone disease, renal impairment, venous thromboembolism, cytopenias, infections and neuropathy are the common complications of MM or its treatment. Novel agents and stem cell transplantation have improved the overall (OS) and progression free survival (PFS). However, it is important to consider the pharmacokinetics, pharmacodynamics, personal preferences, economical concerns and side effect profile of individual drugs while using as a single agent or in combination to avoid further compromising the affected organ system of a susceptible patient. Published literature and guidelines highlight the benefits or disadvantages of particular regimens in patients with specific risk factors such as National Comprehensive Cancer Network, International Myeloma Working group, European Myeloma Working group and Mayo Stratification for Myeloma and Risk-Adapted guidelines. The purpose of this review is to identify and summarize findings from original studies and guidelines for personalized therapy in themanagement of MM.Methods and Results:A comprehensive literature search was carried out using PubMed, EMBASE, Wiley Cochrane library, Scopus, Web of Science, CINAHL, and Clinicaltrials.gov (updated 7-29-2017) for original articles, institutional, national and international guidelines addressing the adjustments of myeloma therapy with a focus on personalized therapy. 129 articles focusing on individualization of therapy for MM patients with renal impairment, risk of venous thromboembolism, high-risk cytogenetics, bone disease, advance age, relapse and plasma cell leukemia are selected and summarized. Articles and guidelines regarding personalization of stem cell transplantation and therapy options after relapse are also summarized in this review.Conclusion:First step towards personalizing the MM therapy is identification of comorbidities (DM, HTN), organ function status (heart, renal failure), disease risk stratification (standard, intermediate, high), transplant eligibility (yes/no), and other risk factors (advanced age, marrow suppression, neuropathy, fluid overload, hyperglycemia). For elderly frail patients, the dosage of all drugs needs to be adjusted considering the age-related compromise of organ systems. Transplant eligibility needs to be considered before using melphalan based induction regimens. Maintenance therapy with novel agents increases OS and PFS but their long term use is associated with drug specific adverse effects. Lenalidomide is associated with bone marrow suppression and second primary malignancies (Kotchetkov et al., 2017). Thalidomide is associated with neuropathy worsening (Mohty, et al., 2010) and emergence of treatment resistant clones. Bortezomib is associated with neuropathy, herpes viral reactivation but is considered superior approach especially for high relapse risk population. In advance renal impairment (RI) patients, thalidomide and lenalidomide can cause hyperkalemia and pancytopenia respectively therefore, may require dose adjustment. Bortezomib is preferred in advanced RI and shows rapid improvement in kidney function. Melphalan and cyclophosphamide dose should be reduced in patients with RI (Dimopoulos et al., 2010). High dose steroids and immune modulators are associated with venous thromboembolism (De Stefano V et al. 2014) therefore, these drugs should be used with risk appropriate (low risk prophylaxis with ASA, high risk with full anticoagulation) prophylaxis. MM patients with high-risk cytogenetics should receive risk adapted bortezomib or carfilzomib based three drug induction therapy and long-term maintenance therapy preferably with a proteasome inhibitor. Bisphosphonate dose in MM patients with RI should be reduced and alternative options should be explored (Denosumab) if necessary. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of treatment delays on vitiligo during the COVID-19 pandemic: A retrospective study.

Due to the COVID‐19 pandemic, routine treatments are delayed to some extent and their negative impacts have been widely reported. However, virtually nothing is known about vitiligo in the context of COVID‐19. Therefore, we analyzed treatment delays and its impact on vitiligo, aiming to provide suggestions on vitiligo management within this special period. We performed a retrospective cohort study on 322 patients who visited our clinics at least 2 times from January to December 2020, and their medical records and photographs were reviewed. Patients were divided into normal (n = 155) and late group (n = 167) based on whether experienced treatment delays. As for the active cases, the late group showed higher progression rate than normal group (35 of 86 [40.7%] vs. 10 of 81 [12.3%]; p = 0.002). Moreover, we observed higher recurrence rate in delay group than those of normal group (26 of 81[32.1%] vs. 9 of 74 [12.2%]; p = 0.018) among stable cases. Further univariate and multivariate analysis determined treatment delays as the most important independent risk factor for disease progression and recurrence, and maintenance therapy (>2 years) as a protective factor against recurrence. This study, for the first time, revealed the independent adverse impact of treatment delays on the progression and recurrence of vitiligo and indicated the significance of continuous treatment for halting progression and long‐term maintenance therapy for preventing recurrence for vitiligo, which should be highly valued in the management of vitiligo during the COVID‐19 pandemic.

MO573CNI AND MTORI-BASED REGIMENS ON FIVE-YEAR COURSE OF BONE MINERAL DENSITY SCORES AFTER RENAL TRANSPLANTATION

Abstract Background and Aims Since glucocorticoids are used in low maintenance doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis after solid organ transplantation has gained clinical significance. In contrast, (mammalian target of rapamycin inhibitors) mTORi agents are shown to have an antiresorptive effect on bone by reducing osteoclastic activity in vitro and in vivo. We investigated the bone mineral density (BMD) changes on an extremely selective group of incident renal transplant recipients under CNI or mTORi-based maintenance treatment regimens during the first five-year posttransplant course. Method This study consists of renal allograft recipients with a dialysis history of less than one year. Patients older than 50 years old, using CNI - mTORi combinations, patients with a history of a prior renal transplant, acute rejection, CNI – mTORi switch after posttransplantation first three months, bisphosphonate treatment, parathyroidectomy, diuretic use, and malignancy excluded to eliminate all confounding factors for bone mineral loss. First and fifth-year BMD scores and simultaneous laboratory parameters were evaluated. Results CNI (n=21) and mTORi (n=17) groups had similar demographics, dialysis vintages, cumulative steroid doses, first and fifth-year parathormone, calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur neck scores of the CNI group decreased from -0.82(±0.96) to -1.52(±0.92) (p=0.020). We observed a significant decrease in the CNI group compared to the mTORi group [-0.70(±0.68) and 0.30(±0.36), respectively; p&amp;lt;0.01] when BMD score changes evaluated among years. The mean femur neck score of the mTORi group insignificantly increased from -1.13(±0.65) to -0.82(±0.56) at the fifth-year DXA scan (p=0.230). Although statistically insignificant, similar trends were also observed in L1-4 scores. Conclusion Our study suggests that CNI-based treatment is associated with decreased femur neck and L1-4 BMD scores, and mTORi-based treatment tends to be beneficial presumably due to their antiresorptive effects in the posttransplant five-year follow-up. Our findings may shed light on long-term maintenance therapy management in renal transplant patients with bone disease if supported by future studies.

One-Year Outcomes of the Open-Label Extension of CHIASMA OPTIMAL, a Phase 3 Study of Oral Octreotide Capsules in Acromegaly

Background: Based on the CHIASMA OPTIMAL study, oral octreotide capsules (OOC) were recently approved in the US as a long-term maintenance therapy for patients with acromegaly previously responding to injectable octreotide or lanreotide, somatostatin receptor ligands (SRLs). Results on longer-term efficacy and safety of OOC from the first 48 weeks of the open-label extension (OLE) of this study are presented here. Methods: Eligible patients had the option to enroll in the OLE of CHIASMA OPTIMAL following the double-blind placebo-controlled (DPC) period; 90% of patients who received OOC in the DPC period enrolled. All patients entering the OLE were initiated on a 60 mg/day dose of OOC and titrated up or down based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. End points in the OLE were exploratory and included the proportion of patients who completed week 48 of the OLE, the proportion who completed as responders (defined as average IGF-I ≤1.0 × upper limit of normal [ULN] at weeks 46/48), and changes in IGF-I from baseline of DPC and OLE until week 48 of the OLE; multiple imputation (MI) was used for missing data. Results: Forty patients entered the OLE (n=20 each; OOC and placebo). Median exposure to OOC in the OLE was > 1 year for those who had been on placebo in the DPC and ≤ 21 months for those who had been on OOC. Dosing of OOC at the end of their participation in the OLE was 40 mg, n=3; 60 mg, n=10; and 80 mg, n=27. In those who received OOC during the DPC, 90% (n=18) completed 48 weeks of the OLE. Of responders at the end of the DPC period (n=14), 92.6% maintained response at OLE week 48. In patients from the OOC group who completed the DPC on study drug, average IGF-I using MI was 0.91 and 0.90 × ULN at OLE baseline and week 48, respectively. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.06 × ULN in patients who completed the DPC on OOC (n=19). In those who received placebo during the DPC, 70% (n=14) completed 48 weeks of the OLE. Of responders at the end of the DPC (n=5), 100% maintained response at OLE week 48. In patients from the placebo group who completed the DPC and did not revert to prior injectable therapy (n=9), the average IGF-I values were 1.09 and 0.87 × ULN at OLE baseline and week 48 respectively, using MI. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.08 × ULN in patients who completed the DPC on placebo (n=9). The most common treatment-emergent adverse events (TEAEs) were gastrointestinal; most were mild or moderate. The incidence of TEAEs was similar between patients who were on OOC or placebo during the DPC. The safety profile during the OLE did not show new concerns with increased duration of drug exposure. Conclusion: Long term maintenance of biochemical response to OOC is durable as assessed following ≤ 21 months of treatment. The OOC safety profile in the extension study is consistent with that of injectable SRLs but without injection-related AEs.

TO EVALUATE THE TRIGGER FACTORS AND HORMONAL ABNORMALITIES IN ADULT FEMALE ACNE

Introduction: Acne is affecting an increasing number of adult females and so can no longer be considered as a disease of adolescence. Genetic and hormonal factors are thought to play key roles in the pathogenesis of adult female acne and the disease is characterized by a chronic evolution with frequent relapses requiring long-term maintenance therapy. Material and Methods: This is a prospective and observational study conducted over a period of 1 year. Patients over the age of 25 years presenting with acne in a tertiary care hospital were included in the study. A detailed history and examination was carried out, with a stress on aggravating factors. Hormonal imbalances were investigated in females with alopecia, obesity, hirsutism and menstrual irregularity. Severity of acne and complications like scarring and psychological stress were included. Results: Out of 90 patients included in the study 100% were women. The mean age of the patients was 31.2 years. Persistent acne was observed in 60%, while it was late onset in 40%. The most common lesion at presentation was papule (63.21%) followed by mixed lesions including pustules, nodules, and comedones. The patient acne severity was graded as mild (80%) to moderate (21%) with a mean GAGS of 13.45 ± 3.63. Facial involvement was seen in all, except two patients in whom only truncal involvement was present. On the face, cheek was the most common site involved (78.8%) followed by chin (58.8%), mandibular area (54.4%), forehead (41.5%) and nose (21.1%). Conclusion:Adult acne is predominant in women, and as compared to adolescent acne is more inflammatory, with involvement of the cheeks and lower half of the face, while comedones are rare.

Sociodemographic and clinical characteristics of patients with long-term remission with buprenorphine / naloxone in opiate use disorder

IntroductionBuprenorphine/Naloxone (BP/NLX) is an effective drug combination used in long-term maintenance therapy in opiate use disorder (OUD). In some studies, abstinence over 180 days was defined as long-term remission (1).ObjectivesThe aim of this study is to determine the sociodemographic and clinical characteristics of patients in long-term remission with BP/NLX.Methods In this study, 30 patients who were followed up with OUD at Akdeniz University Addiction Center and were in remission with BP/NLX for at least 180 days were evaluated retrospectively.ResultsSociodemographic and clinical characteristics are summarized in table 1.ConclusionsOUD is associated with lower quality of life and employment rate (2). In our study, the rate of working in a regular job is high. It can be concluded that prolonged remission improves functionality in patients. Although patients are in remission for a long time in terms of opiate use, 20% of patients continue to use cannabis and 10% continue to use cocaine. In a study, there was no difference in productivity and quality of life between BP users with and without current cannabis use. Continued use of cannabis by patients may be related to this condition. However, cannabis use increases many mental illnesses, especially psychosis (4). In patients in remission with BP/NLX, studies should also be carried out to avoid other substances than opiates. In our study, in accordance with the literature (5), no negative effects on kidney and liver functions were observed with long-term BP/NLX treatment. BP/NLX appears to be safe in prolonged use.DisclosureNo significant relationships.

Atezolizumab in combination with intrathecal chemotherapy and radiation for treatment of isolated cerebral nervous system relapse in a patient with extranodal NK/T cell lymphoma: a case report

BackgroundExtranodal NK/T cell lymphoma (ENKTL) is an aggressive form of Epstein-Barr virus (EBV)-associated non-Hodgkin’s lymphoma which historically has a poor prognosis. When relapse occurs, particularly in the cerebral nervous system (CNS), survival is rare. The immune checkpoint pathway family of proteins is highly expressed in many human tumors, especially in EBV-related malignancies. To the best of our knowledge, there are no reports of immune checkpoint inhibitors used either alone or in combination for the treatment of ENTKL CNS relapse, yet there are promising results in metastatic CNS involvement of other malignancies.Case presentationThis is the case of a 29-year-old Hispanic male with ENKTL who was treated at first relapse with 24 doses of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor, atezolizumab, over a 17-month period. He remained in remission for 18 months until he experienced an isolated CNS relapse and on-going evidence of chronic EBV infection. Salvage therapy was provided as a combination of triple intrathecal (TIT) chemotherapy, radiation, and atezolizumab. He continues on maintenance atezolizumab and remains alive 1-year post CNS relapse.ConclusionsThe results from this case suggest that atezolizumab should be considered as part of the treatment regimen for relapsed ENKTL. They also demonstrate the benefit of using atezolizumab in combination with TIT chemotherapy and radiation as a viable treatment option for ENKTL CNS relapse and indicate that atezolizumab is an option for long-term maintenance therapy for patients with ENKTL.

Consensus recommendation on the use of therapeutic plasma exchange for adult neurological diseases in Southeast Asia from the Southeast Asia therapeutic plasma exchange consortium.

Therapeutic plasma exchange (TPE) is an effective and affordable treatment option in most parts of Southeast Asia (SEA). In 2018, the SEA TPE Consortium (SEATPEC) was established, consisting of regional neurologists working to improve outcome of various autoimmune neurological diseases. We proposed an immunotherapeutic guideline prioritizing TPE for this region. We reviewed disease burden, evidence-based treatment options, and major guidelines for common autoimmune neurological disorders seen in SEA. A modified treatment algorithm based on consensus agreement by key-opinion leaders was proposed. Autoimmune antibody diagnostic testing through collaboration with accredited laboratories was established. Choice of first-line immunotherapies (IVIg/corticosteroid/TPE) is based on available evidence, clinicians’ experience, contraindications, local availability, and affordability. TPE could be chosen as first-line therapy for GBS, CIDP, MG (acute/short term), IgG, A paraproteinemic neuropathy, and NMDAR encephalitis. Treatment is stopped for acute monophasic conditions such as GBS and ADEM following satisfactory outcome. For chronic immune disorders, a therapy taper or long-term maintenance therapy is recommended depending on the defined clinical state. TPE as second-line treatment is indicated for IVIg or corticosteroids refractory cases of ADEM, NMOSD (acute), MG, and NMDAR/LGI1/CASPR2/Hashimoto’s encephalitis. With better diagnosis, treatment initiation with TPE is a sustainable and effective immunotherapy for autoimmune neurological diseases in SEA.

The newer antipsychotic cariprazine (reagila): perspectives for use in different stages of schizophrenia therapy

Cariprazine is a newer 3rd generation antipsychotic acting as partial agonist for dopamine receptors with unique higher affinity for D3 than D2 receptors. This review article summarizes key data from preclinical and clinical studies of cariprazine including pharmacodynamics, pharmacokinetics, clinical efficacy and safety/acceptability in acute short-term and long-term maintenance and relapse prevention therapy in patients with schizophrenia. Efficacy and safety of cariprazine in patients schizophrenia with predominantly negative symptoms resistant to previous antipsychotic therapy is discussed as well.

About diagnosis and therapy of bipolar disorder

The author describes diagnostic criteria and clinical symptoms of bipolar affective disorder (BAD) and summarizes the results of clinical studies on using modern antipsychotics to optimize BAD treatment. Preliminary recommendations for the use of aripiprazole in treatment of BAD, including exacerbation therapy and long-term maintenance therapy to prevent relapses, are presented.