Long-term Maintenance Therapy Research Articles

Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study.

Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

Should complete B cell depletion be maintained in patients treated long-term with rituximab for rheumatoid arthritis?

To determine whether persistent complete B cell (BC) depletion was associated with a better clinical response in rheumatoid arthritis (RA) patients long-term treated with rituximab (RTX). We conducted a retrospective study including RA patients admitted for a new infusion between 2019 and 2021. The primary endpoint was the comparison of the mean disease activity score based on 28 joints (DAS28)-CRP at each of the four last infusion visits between patients with persistent complete BC depletion (mean CD19 counts <18/µl at each of the last four visits) or without persistent complete BC depletion (mean CD19 counts of the last four visits ≥18/µl). Secondary endpoints included DAS28, pain/fatigue visual analogue scale, CRP, gammaglobulins and the frequency of self-reported RA flares. Of the 126 patients in maintenance therapy with RTX [exposure period: 76 (5) months, 14 (7) infusions received], 43 (34%) had persistent complete BC depletion at each of the four last infusions. The mean DAS28-CRP calculated at each of the four last infusion visits did not significantly differ according to persistence or not of complete BC depletion. This result remained unchanged after adjusting for antibody status, number of previous therapies, number of RTX infusion and cumulative RTX dose. All secondary outcomes were also not significantly different between the two groups. Maintaining complete BC depletion does not appear to be a therapeutic target to achieve in RA patients in long-term maintenance therapy with RTX. There is a limited benefit of monitoring CD19 in RA patients long-term treated with RTX and having achieved low disease activity/remission.

Eosinophil values in exacerbation and stable chronic obstructive pulmonary disease and its relationship to maintenance therapy in stable chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) is characterised by persistent and progressive airflow limitations. The study aimed to determine the relationship between eosinophil values in patients with stable and exacerbated COPD, and the relationship of eosinophil values with two drug regimens used as maintenance therapy in stable COPD. This cross-sectional study and the variables used in this study were eosinophil counts in stable and exacerbated COPD patients. Eighty-three patients with stable and exacerbated COPD were included. Stable COPD (63.9%) was predominant, with the highest degree of symptoms in group A 18 patients (34%) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2; 35 patients (66%). The degree of COPD exacerbation was dominated by Type II COPD 15 patients (50%). Eosinophil counts in patients with stable COPD were less than 100cells/mm3 37 patients (44.6%), while in patients with COPD exacerbation, it was greater than 100cells/mm3 with a total of 30 patients (36.1%). Long acting muscarinic antagonist class of drugs was the most used treatment as maintenance therapy in stable COPD 34 patients (64.2%). The eosinophil counts in patients with COPD exacerbation were significantly higher than those in patients with stable COPD. The provision of maintenance therapy in the long acting β-2 agonist + inhaled glucocorticosteroid group of stable COPD patients was generally provided to COPD patients with eosinophil values greater than 100cells/mm3, and the provision of long-term maintenance therapy in stable COPD patients was generally given to COPD patients with eosinophil values less than 100cells/mm3.

„Switch“ z biosimilárního infliximabu CT-P13 na biosimilární infliximab SB-2 v dlouhodobé udržovací terapii IBD pacientů – prospektivní observační studie

Introduction: Therapeutical switch from originator to biosimilar infliximab has been proved as effective and safety procedure. We have a few information about non-medical swich from one biosimilar to the another biosimilar infiximab. Aim: This is a prospective observational study from one tercial IBD center, performed in 2021 and 2022 which was focused on efficacy and safety after switch from infliximab CT-P13 to infliximab SB-2 in patients with IBD. Methods: The cohort group comprised with 287 patients with IBD who have been consecutively treated with infliximab CT-P13 and they were switched to infliximab SB-2. All the re cruited patients were in clinical and biological sustained remission at mean for 6 months before the switch. Results: We proved that persistence on infliximab SB-2 therapy after the switch was 86.4% of treated patients, no significant changes in clinical inflammatory activities and biological parameters have been detected after the switch. The therapy termination due to side effects or loss of response in 39 patients (13.9%) has been detected due to lost of clinical response, side effects or lost of follow-up. No higher immunogenicity after the switch was found. Conclusion: Non-medical switch from one biosimilar infliximab (CT-P13) to another one (SB-2) was not associated with higher risks of disease destabilisation or immunogenicity. Keywords inflammatory bowel disease, biosimilar infliximab CT-P13, biosimilar infliximab SB-2, therapeutical switch

Full mouth rehabilitation of young adults with oligodontia: Two case reports emphasizing implantology, prosthodontics, and restorative intervention

Oligodontia, a severe form of hypodontia characterized by the absence of multiple permanent teeth, presents considerable challenges in dental treatment. Successful management of this condition requires early detection and a comprehensive, multidisciplinary approach. While the complete restoration of missing teeth is typically postponed until all permanent teeth have erupted or after orthodontic therapy, it is crucial to consider additional factors such as the patient's oral hygiene status, socioeconomic circumstances, and long-term maintenance therapy for achieving optimal treatment outcomes. This case reports showcase the effective treatment of oligodontia in two young male patients: a 17-year-old Chinese individual and a 19-year-old Caucasian individual. These cases serve to emphasize the significance of early diagnosis, multidisciplinary collaboration, and personalized treatment planning in addressing the challenges posed by oligodontia. Although orthodontic intervention was not pursued in the presented cases, it is important to recognize its integral role in the overall treatment of oligodontia. The restoration of missing dentition has a profound positive impact on aesthetics, function, and the overall quality of life. The presented cases underscore the importance of early intervention and sustained motivation throughout the treatment process. By emphasizing the value of early detection, comprehensive teamwork, and individualized treatment approaches, clinicians can strive to achieve optimal outcomes for patients with oligodontia.

Multiple Myeloma: Current Clinical Landscape and Compounding Costs.

The treatment landscape of multiple myeloma (MM) has evolved resulting in MM becoming a chronic condition. The costs of MM therapies are substantial and compound as patients remain on long-term maintenance therapies and progress through multiple lines of high-cost therapies. MM predominantly impacts the elderly population insured by Medicare; here, we analyze how these costs impact patients and the Medicare trust fund. With the recent passing of the Inflation Reduction Act (IRA), we postulate how costs may be impacted and debate future policy initiatives that may result in sustainability. The IRA will impact drug pricing and likely reduce the costs of some treatments used in MM; there is still a lot of room for policy reform to reduce financial toxicity to patients and prevent depletion of the Medicare trust fund.

Comparative analysis of the pharmacokinetic parameters of transdermal and injectable forms of nicotinamide

In recent years, oxidative stress, characterized by excess free radicals in the body, has been called the cause of many diseases. There is an active search for drugs with antioxidant properties that are suitable for long-term maintenance therapy. Nicotinamide (NAM), an antioxidant, is used to treat a variety of diseases, usually in oral or injectable form. Given the peculiarities of the drug regimen (dose, prolonged administration), a new dosage form of NAM, a microemulsion-based transdermal patch (TP), containing 20 mg/10 cm2 of NAM, has been proposed.The objective of this work is to compare the pharmacokinetic parameters of intramuscular and transdermal NAM administration in animal experiments for 24 hours.Materials and methods. We used laboratory samples of nicotinamide TP based on a microemulsion-based transdermal delivery emulsion (TDS) with different content of sodium docusate transfer activator. The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 3.5–4.0 kg. Plasma NAM levels of the experimental animals were determined by high-performance liquid chromatography using a specially designed method on NUCLEODUR PFP columns (5 μm, 250 × 4.6 mm) using the mobile phase acetonitrile: deionized water. The samples were preliminarily purified by solid-phase extraction using Chromabond C18 Hydra cartridges.Results. When administered intramuscularly, the maximum blood NAM level was 13.3±1 μg/mL; when NAM transdermal forms were applied in the same dosage with different contents of the transfer activator, the levels did not differ significantly – 3.1 and 3.2 μg/mL. It was shown that in transdermal administration of NAM, concentration of the active substance remained at a constant level for ~6 hours. The bioavailability of NAM with transdermal administration was calculated relative to intramuscular administration: 1.43 for TP with 9.8% docusate sodium and 1.84 with 3.3% docusate sodium.Conclusion. NAM has a higher bioavailability when administered transdermally at 20 mg than when administered intramuscularly in the same dose. With transdermal administration, NAM concentration can be maintained at a constant level for a long time, without the jumps that are typical of intramuscular administration.

Successful Management of Steroid-refractory Morvan's Syndrome 3 Months after Onset with Therapeutic Plasma Exchange

A 52-year-old man presented with behavioral and cognitive symptoms and involuntary movements. Serum CASPR-2 antibodies were strongly positive, and the nerve conduction study showed hyperexcitability. Thus, it was diagnosed as a case of Morvan's syndrome, detected after 3 months. The failed therapy with steroids led to the initiation of the therapeutic plasma exchange (TPE). Five cycles of TPE were completed to improve dramatically the cognitive and behavioral issues as well as the involuntary movements. He was initiated on rituximab for long-term maintenance therapy. In conclusion, TPE can be initiated even after 3 months of onset to achieve significant recovery. Although it is challenging, it is still a tolerated procedure with good outcomes.

Mycophenolate mofetil as induction and long-term maintenance therapy in childhood cerebral vasculitis: a case series.

Journal Article Accepted manuscript Mycophenolate Mofetil as induction and long-term maintenance therapy in childhood cerebral vasculitis: a case series Get access Ilaria Pagnini, Ilaria Pagnini NEUROFARBA Department, Rheumatology Unit, Meyer Children's Hospital IRCCS, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Marzia Mortilla, Marzia Mortilla Meyer Children’s Hospital IRCCS, Florence, ItalyRadiology Search for other works by this author on: Oxford Academic PubMed Google Scholar Diletta Gentile, Diletta Gentile Neuroscience Department, Meyer Children’s Hospital IRCCS, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Ilaria Maccora, Ilaria Maccora NEUROFARBA Department, Rheumatology Unit, Meyer Children's Hospital IRCCS, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Sarah Abu-Rumeileh, Sarah Abu-Rumeileh NEUROFARBA Department, Rheumatology Unit, Meyer Children's Hospital IRCCS, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicola Limbucci, Nicola Limbucci Interventional Neurovascular Unit, A.O.U. Careggi, Italy, Florence Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabriele Simonini, Gabriele Simonini NEUROFARBA Department, Rheumatology Unit, Meyer Children's Hospital IRCCS, University of Florence, Florence, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna Rosati Anna Rosati Neuroscience Department, Meyer Children’s Hospital IRCCS, University of Florence, Florence, Italy Corresponding author. Anna Rosati, MD, PhD, Neuroscience Department, Meyer Children’s Hospital, University of Florence, Viale Pieraccini 24, 50139 Florence, Italy, Email: anna.rosati@meyer.it https://orcid.org/0000-0002-8754-7214 Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, kead237, https://doi.org/10.1093/rheumatology/kead237 Published: 26 May 2023 Article history Received: 01 February 2023 Revision received: 20 April 2023 Accepted: 10 May 2023 Published: 26 May 2023

Once-Daily Crisaborole Ointment, 2%, as a Long-Term Maintenance Treatment in Patients Aged ≥ 3 Months with Mild-to-Moderate Atopic Dermatitis: A 52-Week Clinical Study.

Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥3 months with mild-to-moderate AD involving ≥5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. ClinicalTrials.gov, NCT04040192, 31 July 2019.

Observational study of pimecrolimus 1% cream for prevention of transcutaneous sensitization in children with atopic dermatitis during their first year of life.

Epidermal barrier dysfunction in children with atopic dermatitis can cause transcutaneous sensitization to allergens and allergic diseases. We evaluated the effectiveness of an early-intervention algorithm for atopic dermatitis treatment, utilizing pimecrolimus for long-term maintenance therapy, in reducing transcutaneous sensitization in infants. This was a single-center cohort observational study that enrolled children aged 1-4 months with family history of allergic diseases, moderate-to-severe atopic dermatitis, and sensitization to ≥ 1 of the investigated allergens. Patients who sought medical attention at atopic dermatitis onset (within 10 days) were group 1 "baseline therapy with topical glucocorticoids with subsequent transition to pimecrolimus as maintenance therapy"; patients who sought medical attention later were group 2 "baseline and maintenance therapy with topical glucocorticoids, without subsequent use of pimecrolimus". Sensitization class and level of allergen-specific immunoglobulin E were determined at baseline, and 6 and 12 months of age. Atopic dermatitis severity was evaluated using the Eczema Area and Severity Index score at baseline and 6, 9 and 12 months of age. Fifty-six and 52 patients were enrolled in groups 1 and 2, respectively. Compared with group 2, group 1 demonstrated a lower level of sensitization to cow's milk protein, egg white and house dust mite allergen at 6 and 12 months of age, and a more pronounced decrease in atopic dermatitis severity at 6, 9 and 12 months of age. No adverse events occurred. The pimecrolimus-containing algorithm was effective in treating atopic dermatitis and prophylaxis of early forms of allergic diseases in infants. https://clinicaltrials.gov/ NCT04900948, retrospectively registered, 25 May 2021.

Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes

Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking. To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021. Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes. The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up. Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71). In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status. ClinicalTrials.gov Identifier: NCT02044250.

Managing recurrent otitis externa in dogs: what have we learned and what can we do better?

Recurrent otitis externa is a common problem in dogs. Topical treatment for each flare is successful in the short term, but repeated cycles of inflammation and infection lead to chronic inflammatory changes, pain and aversion, and antimicrobial resistance. These make the flares more frequent and harder to control. Eventually, the changes become irreversible and require a total ear canal ablation/lateral bulla osteotomy or ablative laser surgery. Most ear canal surgery is avoidable if recurrent otitis is properly managed at an earlier stage. This requires a different mindset and approach to these cases, taking advantage of recent research and clinical findings. Most importantly, clinicians must appreciate that all recurrent ear infections in dogs are secondary. To achieve a good long-term outcome, it is essential that all the underlying factors in each case are diagnosed and managed using the primary, secondary, predisposing, and perpetuating framework. This means that the primary condition must be diagnosed and managed, the secondary infection treated, predisposing risks identified and corrected, and the perpetuating factors reversed. Treatment is in 2 phases: induction to get the ears in remission and then long-term maintenance therapy to prevent relapses. Treatment should be appropriate to each dog but will typically involve ear cleaning, topical antimicrobial therapy, and topical or systemic glucocorticoids. Novel treatments for infection and inflammation will offer additional options in the future. Understanding the triggers for recurrent otitis in dogs will help clinicians plan effective management regimens that will make a huge difference to the quality of life of their patients and their owners.

Pediatric Patients with Stage IV Rhabdomyosarcoma Significantly Benefit from Long-Term Maintenance Therapy: Results of the CWS-IV 2002 and the CWS DOK IV 2004-Trials

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma (STS) in childhood. Whereas more than 90% of patients with localized low-risk RMS can be cured, metastatic RMS have a dismal outcome, with survival rates of less than 30%. The HD CWS-96 trial showed an improved outcome for patients receiving maintenance therapy after completing intensive chemotherapy. Consequently, the international clinical trials CWS-IV 2002 and CWS DOK IV 2004 on metastatic disease of STS of the Cooperative Weichteilsarkom Studiengruppe (CWS) were designed in addition to the CWS-2002P trial for localized RMS disease. All patients received a multimodal intensive treatment regimen. To maintain remission, three options were compared: long-term maintenance therapy (LTMT) versus allogeneic hematopoietic stem cell transplantation (alloHSCT) versus high-dose chemotherapy (HDCT). A total of 176 pediatric patients with a histologically confirmed diagnosis of metastatic RMS or RMS-like tumor were included. A total of 89 patients receiving LTML showed a significantly better outcome, with an event-free survival (EFS) of 41% and an overall survival (OS) of 53%, than alloHSCT (n = 21, EFS 19%, p = 0.02, OS 24%, p = 0.002). The outcome of LTML was slightly improved compared to HDCT (n = 13, EFS 35%, OS 34%). In conclusion, our data suggest that in patients suffering from metastatic RMS, long-term maintenance therapy is a superior strategy in terms of EFS and OS compared to alloHSCT. EFS and OS of HDCT are similar in these strategies; however, the therapeutic burden of LTMT is much lower.

Hypogonadism: cardiometabolism and gonadal function in men

Hypogonadism is a relatively rare condition in men, which increases in frequency as men age, but also as they become less active and gain weight. In the past 20 years, developing knowledge on the relationship between hypogonadism and cardiovascular and cerebrovascular health and on aspects of metabolic health has become clearer. The relationship between hypogonadism and specific endocrine abnormalities of spermatogenesis is much longer established. Long- and short-term testosterone replacement therapies have well-recognised effects on cardiovascular and cerebrovascular health and on aspects of metabolic health. This leads to a sense of safety when it comes to considering these options as ways of managing the recognised symptoms of hypogonadism and the hidden adverse findings. That confidence has yet to be proven by long-term randomised controlled studies. The use of exogenous gonadotrophins to raise endogenous testosterone levels is a cost-efficient method of achieving spermatogenesis but is not suitable for long-term testosterone maintenance therapy.

Evidence-base for the beneficial effect of nutraceuticals in canine dermatological immune-mediated inflammatory diseases - A literature review.

Immune-mediated inflammatory diseases (IMIDs) are associated with an abnormal immune response, resulting in a disturbed homeostasis and chronic inflammation. Most canine dermatological IMIDs (cDIMIDs), such as allergies, autoimmune and immune-mediated diseases, require long-term treatment with immunosuppressive drugs with potential adverse effects. In general, nutraceuticals are thought to be safe. As a result, there is a tendency for the more frequent use of nutraceuticals in veterinary medicine. The aim of this review was to present evidence-based proof for the use of various nutraceuticals in the treatment of cDIMIDs and, where possible, to provide conclusions to guide their use in veterinary dermatological practice. A comprehensive literature search on common cDIMIDs and nutraceuticals was performed. Only peer-reviewed articles published in English and related to the study topic were included. A total of 64 eligible publications were classified in five categories based on study design and substantively assessed on additional criteria such as standardisation of diets and number of included animals. For final appraisal, classification of major, minor or no evidence was used whereby efficacy was based on clinical outcome measurements. Minor evidence for the beneficial use of several nutraceuticals, including essential fatty acids, niacinamide and probiotics, was found for treatment of specific cDIMIDs. These nutraceuticals may improve clinical signs or reduce the required dose of concurrent medication (e.g. drug-sparing effect) in some dogs. Some nutraceuticals also may be used for long-term maintenance therapy. Despite some promising findings, major evidence for the use of nutraceuticals in cDIMIDs is lacking, warranting further research.

Predictors of damage accrual in patients with antineutrophil cytoplasmic antibody-associated vasculitis: A nationwide prospective study.

This study elucidated the prognosis and risk factors associated with damage accrual during long-term remission maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). We obtained data from 120 patients registered in a nationwide prospective cohort study on remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN), who achieved remission at 24 months after treatment initiation and were followed up for additional 24 months. The primary outcome was the vasculitis damage index (VDI) score at Month 48, and the secondary outcome included risk factors associated with increased total VDI at Month 48. The understudied patients comprised 52 men and 68 women aged 68 ± 13 years. Between Months 25 and 48, the patients' survival rate was 95% (114/120). End-stage renal disease developed in seven patients by Month 48, and 64 cases had increased VDI. The multivariable analysis results revealed that oral prednisolone (PSL) doses at Month 24 were associated with damage accrual between Months 24 and 48. VDI accrual was observed in more than half of patients with AAV during maintenance therapy, and increased VDI scores were associated with oral PSL doses 24 months after initiating remission induction therapy in Japan.

Real-world data for lenalidomide maintenance in responding patients of diffuse large B-cell lymphoma.

Approximately 40% patients of diffuse large B-cell lymphoma (DLBCL) would develop disease recurrence/progression after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single-drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti-tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long-term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R-CHOP treatment. This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6-8cycles of R-CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n=141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n=50) and drug-free maintenance treatment (control, n=91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression-free survival (PFS) was taken as the primary outcome. Of the total 141 subjects, the median follow-up time was 30.9months (range, 5.7-68.9months). The 2-year PFS was 84% (95% CI: 74%-94%) in the lenalidomide group and 53% (95% CI: 43%-63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9months (HR=0.32; 95% CI: 0.16-0.63; p=0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR=0.42; 95% CI: 0.16-1.12; p=0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1-2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3-4 adverse reaction. Two-year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first-line R-CHOP treatment.

2 grams versus 1 gram rituximab as maintenance schedule in multiple sclerosis, neuromyelitis optica spectrum disorders and related diseases: What B-cell repopulation data tell us.

Rituximab (RTX) is largely used as a long-term maintenance therapy in various inflammatory neurological diseases. Reducing the dose of maintenance therapy of RTX from 2 grams every 6 months (traditional regimen) to 1gram every 6 months (reduced regimen) is a widely applied practice, with the assumption that it decreases the risk of side effects while maintaining efficacy. In order to better describe the biological consequences of this strategy, we retrospectively compared, in a single center, the B-cell count after the traditional regimen and after the reduced regimen in patients who underwent both (n=161). The rate of patients with B-cell repopulation was not significantly different between traditional and reduced regimens (9.9% vs 15.6%, p=0.18). Among the 145 patients who did not have B-cell repopulation following the traditional regimen, B-cell repopulation following the reduced regimen occurred in only 16 cases (11.0%) and was usually slight: 11/16 patients had only 1% of CD19+ cells. These data emphasize the relevance of 1g of RTX as maintenance therapy and the fact that 2g of RTX is generally an overtreatment in inflammatory neurological diseases.

IgG4-related autoimmune liver disease.

The term IgG4-related autoimmune liver disease (AILD) refers to hepato-biliary manifestations of Immunoglobin G4-related disease (IgG4-RD) including IgG4-related sclerosing cholangitis and IgG4-related pseudotumor. The association of some forms of autoimmune hepatitis to IgG4-RD remains controversial. Although autoimmune phenomena have not been clearly observed in IgG4-AILD, perturbation of the adaptive immune system and activation of the humoral response represent established pathophysiological hallmarks and potential therapeutic targets. Clinical manifestations of IgG4-AILD are virtually indistinguishable from bile duct cancer or primary sclerosing cholangitis and are due to mass forming lesions and thickening of the biliary tract that progressively lead to biliary ducts obstruction. There are no current reliable biomarkers for IgG4-AILD and diagnosis should rely on the integration of clinical, serological, radiological, and histological findings. In analogy to most IgG4-RD manifestations, and in contrast to its major mimickers, IgG4-AILD promptly responds to glucocorticoids but frequently relapses, thus requiring long-term maintenance therapy to avoid progressive fibrosclerotic disease and liver cirrhosis. Accumulating evidence on the efficacy of B-cell depletion therapy in patients with systemic IgG4-RD is gradually changing the treatment paradigm of IgG4-AILD and biologics will be increasingly used also for gastroenterological manifestations of IgG4-RD to spare glucocorticoids and traditional immunosuppressive agents. Looking ahead, identification of reliable biomarkers and of mini-invasive strategies to obtain informative biopsies from the biliary tree represent unavoidable priorities to optimize diagnosis and management of IgG4-AILD.