Immunomodulator adherence in multiple myeloma patients with lower socioeconomic status: a retrospective study.

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.

Burden of treatment and quality of life in relapsing remitting multiple sclerosis patients under early high efficacy therapy in Argentina: Data from the Argentinean registry.

The objective of this study was to describe and compare the burden of treatment (BOT) and the quality of life (QoL) in early high efficacy therapy (HET) vs. escalation therapy in relapsing remitting multiple sclerosis (RRMS) patients included in RelevarEM, the Argentinean registry of MS (RelevarEM, NCT 03,375,177). METHODS: cross sectional study conducted between September and December 2022. Participating patients were adults, RRMS patients who initiated (during the last three years) their treatment with a HET (natalizumab, ocrelizumab, alemtuzumab, cladribine) or with escalation treatment (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate or fingolimod). Clinical and demographic aspect were collected. QoL and BOT was measured with the validated to Spanish MusiQol and BOT questionnaire. Propensity score (PS)-based nearest-neighbor matching was applied to homogenize groups. Comparisons were be done using a linear regression analysis model stratified by matched pairs, with BOT and QoL assessments as main outcomes. RESULTS: 269 patients were included in the analysis, mean age 33.7 ± 5.7 years, 193 (71.7 %) were female. A total of 136 patients were on early HET while 133 were on escalation therapy. In the entire group the mean total BOT score (±SD) was 48.5 ± 15.3 while in the group of patients receiving early HET we observed that the mean BOT score (±SD) was 43.5 ± 12.2 vs. 54.3 ± 13.3 in escalation treatment (p < 0.0001). Regarding the score QoL (±SD), in the entire sample we observed a global score of 77.4 ± 11.2. When we stratified groups, in HET (±SD) it was 81.3 ± 14 vs. 74.1 ± 18.3 in escalation therapy (p = 0.0003). CONCLUSION: in this multicenter study that included 269 patients from Argentina we observed in early HET a significantly lower BOT and higher QoL than patients receiving escalation therapy.

[Therapeutic Strategies and Disease-Modifying Therapies for Multiple Sclerosis].

Multiple sclerosis is an inflammatory demyelinating disease of unknown cause that affects the central nervous system. Although it was once deemed "incurable," many disease-modifying therapies have been introduced since the beginning of the 20th century; eight of these are now available in Japan. Treatment for multiple sclerosis is undergoing a significant shift from the safety-oriented "escalation strategy," in which the patient is initially administered medications with low risks of side effects but moderate efficacy, to a "personalized approach" based on individual prognostic factors followed by an "early top-down strategy" in which higher efficacy treatments are initiated first. Disease-modifying drugs for multiple sclerosis can be high- (fingolimod, ofatumumab, natalizumab) or moderate-efficacy (interferon beta, glatiramer acetate, dimethyl fumarate), and there are also disease-modifying therapies for secondary progressive multiple sclerosis (siponimod and ofatumumab). Approximately 20,000 Japanese patients have multiple sclerosis, and this number continues to increase. Many neurologists are expected to prescribe high-efficacy drugs in the future. The risk management of adverse events, particularly progressive multifocal leukoencephalopathy, is required to ensure that the importance of safety never be underestimated, even though treatment efficacy is the main focus.

A safety review of biologic therapies for the management of hidradenitis suppurativa and unmet needs.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by nodules, abscesses, fistulae, and significant scarring in intertriginous areas rich in apocrine glands. Immunomodulator drugs, including biologics, are a mainstay of treatment for this disease. AREAS COVERED: This review details the safety profiles of various biologic therapies currently available commercially that have been tried for HS as assessed in clinical trials and observational studies. As the only Food and Drug Administration (FDA)-approved medication for the treatment of moderate-to-severe HS, adalimumab is discussed in the most detail. Additional biologic medications, including tumor necrosis factor α (TNFα) inhibitors, interleukin 1 (IL-1) inhibitors, IL-12 and IL-23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors, are discussed as well. Safety concerns in special populations, including pregnant women and children, are outlined. EXPERT OPINION: Existing data support excellent short-term and long-term safety profiles for adalimumab, although caution must be taken with use in high-risk patient populations, including those with chronic infections or increased risk of malignancy. Based on their safety data for other indications, additional biologic agents appear safe in HS as well. However, further research is needed to fully understand the safety profiles of these medications in the HS population.

Managing high-priced biologic agents: challenges and potential solutions.

DISCLOSURES: No funding was received for the writing of this commentary. The authors report no conflicts of interest.

The effectiveness and value of targeted immune modulators for moderate to severe ulcerative colitis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Pandey, Fazioli, and Pearson are employed by ICER. Ollendorf reports grants from ICER related to this study and reports other support from the CEA Registry Sponsors and consulting and advisory board fees from EMD Serono, Amgen, Analysis Group, Aspen Institute/University of Southern California, GalbraithWight, Cytokinetics, Sunovion, University of Colorado, the Center for Global Development, and Neurocrine, unrelated to this work. Bloudek reports grants from ICER related to this work and reports fees from AbbVie, Astellas, Akcea, Dermira, GlaxoSmithKline, Sunovion, Seattle Genetics, TerSera Therapeutics, and Incyte, unrelated to this work. Carlson reports grants from ICER related to this work.

Subepithelial autoimmune bullous dermatoses disease activity assessment and therapy.

Subepidermal (subepithelial) autoimmune blistering dermatoses are a group of rare skin disorders characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The fourth article in this continuing medical education series presents the current validated disease activity scoring systems, serologic parameters, treatments, and clinical trials for bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus, anti-p200 pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.

Assessment and Management of Cardiotoxicity in Hematologic Malignancies.

With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.

Persistence and adherence to ocrelizumab compared with other disease-modifying therapies for multiple sclerosis in U.S. commercial claims data.

BACKGROUND: Ocrelizumab (OCR) is the only disease-modifying therapy (DMT) for both relapsing and primary progressive forms of multiple sclerosis (MS). OCR is given by intravenous (IV) infusion twice a year, which may improve adherence to the dosing schedule relative to other MS DMTs that require more frequent administration. Real-world evidence on the persistence and adherence of patients with MS to OCR compared with other DMTs is limited. OBJECTIVE: To examine the persistence and adherence to OCR compared with other DMTs for MS in the United States. METHODS: This analysis was conducted in the PharMetrics Plus commercial claims database and included patients with MS who initiated a new DMT between April 2017 and September 2018. Patients were required to have health plan enrollment for ≥ 1 year before and after DMT initiation (a subgroup analysis was performed for those with ≥ 18 months' continuous enrollment after DMT initiation). Persistence was defined as not switching to another DMT and having no gap in coverage of the initiated DMT for ≥ 60 days during the postinitiation period. The proportion of days covered (PDC) was calculated as the total days covered by the DMT during the postinitiation period divided by the length of the time period (12 or 18 months); PDC ≥ 0.8 was considered adherent. Multivariable Poisson regression models compared discontinuation (nonpersistence) and nonadherence between OCR users and users of other DMTs grouped by administration route. RESULTS: A total of 4,587 patients (OCR, 1,319; injectable, 1,051; oral, 1,876; other IV, 341) were included. The OCR group had the lowest proportion of patients discontinuing at 12 months (8% vs. 28%, 32%, and 43% for other IV, oral, and injectable, respectively) and the highest mean PDC (93% vs. 76%, 74%, and 69%, respectively). Compared with patients initiating OCR, adjusted relative risks (RR) of 12-month discontinuation were 3.3 (95% CI = 2.3-4.6), 3.8 (95% CI = 3.0-4.9), and 5.5 (95% CI = 4.1-7.5) for patients initiating other IV, oral, and injectable DMTs, respectively. Similarly, patients initiating other IV, oral, and injectable DMTs had RRs of 4.9 (95% CI = 3.6-6.8), 5.1 (95% CI = 3.9-6.6), and 6.8 (95% CI = 5.0-9.3) for 12-month nonadherence compared with OCR. A subgroup of 2,913 patients with 18 months of continuous enrollment had similar trends, with 17% in the OCR group discontinuing compared with 40%, 41%, and 55% in the other IV, oral, and injectable groups, respectively. Trends over 18 months were consistent with the 12-month analysis in adjusted models. CONCLUSIONS: Patients initiating OCR had superior persistence and adherence at 12 and 18 months of follow-up compared with patients initiating other MS DMTs. Long-term persistence and adherence should be monitored as OCR experience accrues in a real-world setting. DISCLOSURES: This study was funded by Genentech (South San Francisco, CA), a member of the Roche Group. Engmann, Sheinson, Bawa, and Ng are employees of Genentech and shareholders of F. Hoffman-La Roche (Basel, Switzerland).

Inclusion of the Symbol Digit Modalities Test in a revised assessment of 'no evidence of disease activity-4 (NEDA-4)' in Latin-American patients with multiple sclerosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), no evidence of disease activity-3 (NEDA-3) is defined as the absence of: (1) relapses; (2) disability progression; (3) MRI activity (new/enlarged T2 lesions and/or gadolinium-enhanced T1 lesions). NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized percentage brain volume change (a-PBVC) >-0.4%. In individual patients, brain volume assessment is confounded with normal aging, methodological limitations and fluid-shift related fluctuations in brain volume. Cognitive impairment has been proposed as another component that should be integrated into therapeutic algorithms for RRMS. We aim to determine the proportion of patients failing to meet NEDA-4 criteria and to appraise whether the Symbol Digit Modalities Test (SDMT) is capable of replacing a-PBVC as one of the components of NEDA-4. We hypothesize that NEDA-4 has the potential to capture the impact of DMT therapies in RRMS. METHODS: Forty-five patients were prospectively followed 1 and 2 years after their baseline assessment at the University of Chile Hospital. SIENA software was used to assess a-PBVC. RESULTS: At baseline, the patients had a mean age of 33.0 years (range 18-57), disease duration of 1.9 years (0.4-4), Expanded Disability Status Scale score of 1.3 (0-4), and 67% were female. The majority had RRMS (91% while 9% had clinically isolated syndrome (CIS)). Seventy-three percent were on the so-called first line DMTs such as interferons (53%), glatiramer acetate (13%), teriflunomide (9%), and 18% were on fingolimod. There was a serial decline in the proportion of NEDA: after 1 and 2 years of follow-up 60% and 47% met NEDA-3 status, and 38% and 27% met NEDA-4, respectively. At the last follow-up 21% remained on interferons, 47% were now on fingolimod, 4% on alemtuzumab and 2% on natalizumab. At year 1 and year 2, with the replacement of a-PBVC by SDMT, 53% and 40% of patients achieved a putative NEDA-4 status, respectively. CONCLUSION: Brain volumetric MRI has yet to be translated into clinical practice and SDMT may qualify as the fourth component of NEDA-4 definition. NEDA-4 has the potential to capture the impact of DMT therapies in RRMS earlier in the disease course of RRMS.

Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development.

Vaccination is one of the most important prevention tools providing protection against infectious diseases especially in children below the age of five. According to estimates, more than 5 million lives are saved annually by the implementation of six standard vaccines, including diphtheria, hepatitis B, Haemophilus influenza type b, polio, tetanus and yellow fever. Despite these efforts, we are faced with challenges in developing countries where increasing population and increasing disease burden and difficulties in vaccine coverage and delivery cause significant morbidity and mortality. Additionally, the high cost of these vaccines is also one of the causes for inappropriate and inadequate vaccinations in these regions. Thus, developing cost-effective vaccine strategies that could provide a stronger immune response with reduced vaccination schedules and maximum coverage is of critical importance. In last decade, different approaches have been investigated; among which live bacterial vaccines have been the focus of attention. In this regard, probiotic lactic acid bacteria have been extensively studied as safe and effective vaccine candidates. These microorganisms represent the largest group of probiotic bacteria in the intestine and are generally recognised as safe (GRAS) bacteria. They have also attracted attention due to their immunomodulatory actions and their effective role as novel vaccine adjuvants. A significant property of these bacteria is their ability to mimic natural infections, while intrinsically possessing mucosal adjuvant properties. Additionally, as live bacterial vaccines are administered orally or nasally, they have higher acceptance and better safety, but also avoid the risk of contamination due to needles and syringes. In this review, we emphasise the role of probiotic Lactobacillus strains as putative oral vaccine carriers and novel vaccine adjuvants.

Dose Escalation Assessment Among Targeted Immunomodulators in the Management of Inflammatory Bowel Disease.

BACKGROUND: The need for individualized treatment regimens is becoming more important in the management of patients with inflammatory bowel disease (IBD). Gastroenterologists may dose adjust either by increasing the dose or shortening the dosing interval from the initial recommended maintenance dose to achieve an appropriate clinical response. Understanding the role of dose escalation in the treatment of IBD in clinical practice provides payers in the United States insight into the real-world cost-effectiveness of targeted immunomodulators (TIMs) in the management of IBD. OBJECTIVE: To assess the prevalence and magnitude of dose escalation for approved IBD therapies. METHODS: Using the Source Healthcare Analytics database, patients with IBD who initiated treatment with a drug of interest from July 2015 to June 2017 were identified. Patient utilization of the TIMs was tracked for 12 months following initiation. All included patients had at least 2 diagnoses for ulcerative colitis or Crohn disease before TIM initiation and at least 5 claims for a drug of interest within the 12 months following initiation. Dose escalation was defined as an increase of at least 30% in the average daily dose (ADD) relative to the patient's expected maintenance dose on 2 consecutive prescriptions. The proportion of patients with dose escalation in the first 12 months after treatment initiation was determined. The magnitude of dose escalation was determined by calculating the patient's ADD across all noninduction dose claims and comparing it with the expected daily dose. Dose escalation prevalence and magnitude were used to quantify the equivalent patient treatment rate representing the number of patients per 100 that could have been treated with standard dosing, given the prevalence of dose escalation in the treated population. RESULTS: 7,028 patients (2,406 infliximab, 1,966 adalimumab, 1,745 vedolizumab, 472 ustekinumab, 285 certolizumab pegol, and 154 golimumab) met eligibility criteria and were included in the study. Among IBD therapies, dose escalation occurred most frequently with infliximab (39%), followed by adalimumab (28%), vedolizumab (23%), ustekinumab (22%), certolizumab pegol (20%), and golimumab (14%). The magnitude of dose escalation was greatest for ustekinumab (131%), followed by infliximab (70%), vedolizumab (62%), adalimumab (59%), certolizumab pegol (50%), and golimumab (45%). The calculated patient equivalence was highest for infliximab (128) and ustekinumab (128) compared with adalimumab (116), vedolizumab (114), certolizumab pegol (110), and golimumab (106). CONCLUSIONS: Among patients with IBD, dose escalation occurred with all TIMs examined with varying degrees of prevalence and magnitude. Real-world utilization patterns of TIMs indicate that dose escalation is an important part of the clinical management of IBD and needs to be considered when evaluating the cost-effectiveness of IBD treatments. DISCLOSURES: Financial support for this study was provided by AbbVie, which participated in study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Ehrenberg and McDonald are employees of IQVIA, which received funding from AbbVie to participate in this research. Griffith and Theigs are employed by AbbVie and may own stock or stock options in AbbVie.

Multiple modality approach to assess adherence to medications across time in Multiple Sclerosis.

BACKGROUND: Medication adherence is especially challenging in a chronic condition such as Relapsing Multiple Sclerosis (RMS). Medication adherence among persons with MS (PwMS) is usually assessed via a single measure, mostly electronic pharmacy records. OBJECTIVES: Assess medication adherence in multiple modes across time among PwMS; examine consistency across time and associations between measures. METHODS: PwMS (N = 194) were surveyed prospectively at three time points (baseline, 6 and 12 months later) and their health records and medication claims were retrospectively obtained. Adherence score was based on medication possession ratio (MPR) and two patient-reported outcome (PRO) measures. Electronic monitoring devices assessing medication adherence were also initiated. RESULTS: MPR of each nonadherent PwMS, once compared to medical records containing prescription changes, was found as underestimating adherence. MPR was between the two PROs in identifying nonadherence and associations between the measures and across time was moderate (Kappa ranged 0.37-0.42). The use of electronic monitoring devices was not adopted by patients. A score indicated adherence as 66% and 64.9% at Time1 and Time 2, respectively, with 21.1% of PwMS nonadherent at both time points. Adherence did not vary significantly by DMT type. CONCLUSIONS: Being a dynamic behavior, medication adherence should be repeatedly monitored by using multiple modalities and focused on in clinician-patient encounters, especially in chronic diseases such as MS, which requires long-term treatments. Applying PROs in monitoring medication adherence would facilitate implementation of Participatory Medicine and patient-centered strategies in MS care.

Prevalence of cervical HPV and attitude towards cervical screening in IBD patients under immunomodulatory treatment: a multidisciplinary management experience.

OBJECTIVE: Therapeutic strategies for Inflammatory Bowel Diseases (IBD: Crohn's disease and Ulcerative Colitis) have improved but the risk for HPV infection in patients under immunomodulatory/biologic treatment is unclear. Objective of the study is to identify the attitude of patients and caregivers to cervical screening. To determine the prevalence of HPV and cervical lesions in IBD patients receiving immunomodulatory/biological treatment. PATIENTS AND METHODS: IBD patients treated with immunomodulators were enrolled from November 2016 to September 2017, thanks to a multidisciplinary cooperation. A survey was administered to enrolled patients as well as to a selected network of IBD expert physicians. Patients who consented underwent gynecological examination, smear, HPV DNA test, colposcopy, vaginal and cervical microbiological swabs. RESULTS: 294 patients from AMICI Onlus Association, 119 patients from the hospital clinic, 30 doctors from national IBD centers participated to the survey. 19 patients from the IBD clinic underwent cervical screening. More than 90% of doctors consider their patients at risk of cervical cancer. A low prevalence of high-risk genotypes and related HPV lesions and an increased prevalence of bacterial vaginosis emerged in the studied population. CONCLUSIONS: Biological drugs could lead to a positive immunomodulation towards HPV infection. In IBD patients an alteration of the vaginal and intestinal microbiota seems to be coexisting.

Oral Oncology Parity Laws, Medication Use, and Out-of-Pocket Spending for Patients With Blood Cancers.

BACKGROUND: In this study, we sought to estimate the association between oral oncology parity law adoption and anticancer medication use for patients with chronic myeloid leukemia or multiple myeloma. METHODS: This was an observational study of administrative claims from 2008 to 2017. Among individuals initiating tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia or immunomodulatory drugs for multiple myeloma, we compared out-of-pocket spending, adherence, and discontinuation before and after parity among individuals in fully insured plans (subject to parity) vs self-funded plans (exempt from parity) using propensity-score weighted difference-in-differences regression models. RESULTS: Among patients initiating TKIs (N = 2082) or immunomodulatory drugs (N = 3326) there were no statistically significant differences in adherence or discontinuation associated with parity. The proportion of patients with initial out-of-pocket payments of $0 increased in fully insured plans after parity from 5.7% to 46.1% for TKIs and from 10.9% to 48.8% for immunomodulatory drugs. Relative to changes in self-funded plans, those in fully insured plans were 4.27 (95% CI = 2.20 to 8.27) times as likely to pay nothing for TKIs and 1.96 (95% CI = 1.40 to 2.73) times as likely to pay nothing for immunomodulatory drugs after parity. Similarly, the proportion paying more than $100 decreased from 30.3% to 24.7% for TKIs and 30.6% to 27.5% for immunomodulatory drugs in fully insured plans after parity. Relative to changes in self-funded plans, those in fully insured plans were 0.74 (95% CI = 0.54 to 1.01) times as likely to pay more than $100 for TKIs and 0.85 (95% CI = 0.68 to 1.06) times as likely to pay more than $100 for immunomodulatory drugs after parity. CONCLUSIONS: Among patients initiating TKIs or immunomodulatory drugs, parity was not associated with better adherence or less discontinuation of therapy but yielded decreased patient out-of-pocket payments for some patients.

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

BACKGROUND: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk. OBJECTIVE: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials. METHODS: CAMMS223 and Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week. Patients completing core studies could enroll in an extension. Monthly monitoring for ITP continued until 48 months after the last alemtuzumab infusion. RESULTS: Of 1485 alemtuzumab-treated MS patients in the clinical development program, 33 (2.2%) developed ITP (alemtuzumab 12 mg, 24 [2.0%]; alemtuzumab 24 mg, 9 [3.3%]) over median 6.1 years of follow-up after the first infusion; most had a sustained response to first-line ITP therapy with corticosteroids, platelets, and/or intravenous immunoglobulin. All cases occurred within 48 months of the last alemtuzumab infusion. Postmarketing surveillance data suggest that the ITP incidence is not higher in clinical practice than in clinical trials. CONCLUSION: Alemtuzumab-associated ITP occurs in approximately 2% of patients and is responsive to therapy. Careful monitoring is key for detection and favorable outcomes.

Sensitive Skin Syndrome: An Update.

Sensitive skin syndrome is a widely reported complaint but a diagnostic challenge because of its subjective symptoms and lack of clearly visible manifestations. Epidemiological studies have shown the prevalence of sensitive skin to be as high as 60-70% among women and 50-60% among men. Patients with this syndrome usually have unpleasant sensations when exposed to physical, thermal, or chemical stimuli that normally cause no provocation on healthy skin. Recent studies and newly accepted position papers have provided a more in-depth understanding and consensus of its underlying pathophysiology, associations, diagnosis, and treatment. Since no clinical studies have been conducted about specific treatment protocols, patients with this condition should be provided with personalized skin management. Given this updated knowledge, our review offers an approach to sensitive skin syndrome, with differential diagnoses, and interventions targeting its pathophysiology.

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

Overview of rabies post-exposure prophylaxis access, procurement and distribution in selected countries in Asia and Africa, 2017-2018.

BACKGROUND: Rabies is a neglected zoonotic disease with a global burden of approximately 59,000 human deaths a year. Once clinical symptoms appear, rabies is almost invariably fatal; however, with timely and appropriate post-exposure prophylaxis (PEP) consisting of wound washing, vaccine, and in some cases rabies immunoglobulin (RIG), the disease is almost entirely preventable. Access to PEP is limited in many countries, and when available, is often very expensive. METHODS: We distributed a standardized assessment tool electronically to a convenience sample of 25 low- and middle-income countries in Asia and Africa to collect information on rabies PEP procurement, forecasting, distribution, monitoring and reporting. Information was collected from national rabies focal points, focal points at the World Health Organization (WHO) country offices, and others involved in procurement, logistics and distribution of PEP. Because RIG was limited in availability or unavailable in many countries, the assessment focused on vaccine. Data were collected between January 2017 and May 2018. RESULTS: We received responses from key informants in 23 countries: 11 countries in Asia and 12 countries in Africa. In 9 of 23 (39%) countries, rabies vaccine was provided for free in the public sector and was consistently available. In 10 (43%) countries, all or some patients were required to pay for the vaccine in the public sector, with the cost of a single dose ranging from US$ 6.60 to US$ 20/dose. The primary reason for the high cost of the vaccine for patients was a lack of funding at the central level to subsidize vaccine costs. In the remaining 4 (17%) countries, vaccine was provided for free but was often unavailable so patients were required to purchase it instead. The majority of countries used the intramuscular route for vaccine administration and only 5 countries exclusively used the dose-sparing intradermal (ID) route. Half (11/22; 50%) of all countries assessed had a standardized distribution system for PEP, separate from the systems used for routine childhood vaccines, and almost half used separate storage facilities at both central and health facility levels. Approximately half (9/22; 41%) of all countries assessed reported having regular weekly, monthly or quarterly reporting on rabies vaccination. CONCLUSIONS: While all countries in our assessment had rabies vaccines available in the public sector to some extent, barriers to access include the high cost of the vaccine to the government as well as to patients. Countries should be encouraged to use ID administration as this would provide access to rabies vaccine for many more people with the same number of vaccine vials. In addition, standardized monitoring and reporting of vaccine utilization should be encouraged, in order to improve data on PEP needs.

Treatment Patterns and Clinical and Economic Outcomes in Patients With Newly Diagnosed Multiple Myeloma Treated With Lenalidomide- and/or Bortezomib-containing Regimens Without Stem Cell Transplant in a Real-world Setting.

BACKGROUND: Real-world data in patients with newly diagnosed multiple myeloma (NDMM) are sparse. Using United States claims databases, we analyzed treatment patterns, clinical outcomes, and health care utilization and costs in patients receiving lenalidomide- and/or bortezomib-containing therapy. MATERIALS AND METHODS: Patient claims were obtained from a large commercial and Medicare database (October 2009 to May 2015). Patients with NDMM who received lenalidomide- and/or bortezomib-containing therapy and did not receive stem cell transplant (SCT) were analyzed. Duration of treatment (DOT), time to next treatment (TTNT), and health care utilization and costs were evaluated. RESULTS: Of 3075 patients, 1767 received doublet therapy (814 lenalidomide-dexamethasone [Rd], 953 bortezomib-dexamethasone [Vd]) and 464 received triplet therapy (318 lenalidomide-bortezomib-dexamethasone [RVd], 146 cyclophosphamide-bortezomib-dexamethasone [CyBord]). Rd versus Vd resulted in longer median DOT (12.0 vs. 5.9 months; P < .0001) and median TTNT (36.7 vs. 24.4 months; P = .0005). Year 1 costs were greater with Rd versus Vd (Δ = $14,964; P = .0009), primarily owing to higher pharmacy costs; outpatient physician visits and chemotherapy administration costs were lower. Median DOT (14.8 vs. 9.0 months; P < .0001) and median TTNT (35.7 vs. 22.3 months; P = .0007) were longer with RVd versus CyBord; year 1 costs were comparable. CONCLUSIONS: In this study of patients with NDMM ineligible for transplant, the median duration of therapy was approximately 70% of that in clinical trial observations. Lenalidomide therapy versus Vd and CyBord resulted in longer DOT, which correlated with longer TTNT, and higher pharmacy costs, which were partially offset by lower outpatient and chemotherapy administration costs.