Achieve Disease Remission Research Articles

O05 Active Bechet's with life threatening arterial disease, complicated by concurrent COVID-19 infection at the peak of the COVID-19 pandemic: did immunosuppression help or hinder?

O05 Active Bechet's with life threatening arterial disease, complicated by concurrent COVID-19 infection at the peak of the COVID-19 pandemic: did immunosuppression help or hinder?

Predictors of long-term clinical remission in rheumatoid arthritis.

Little is known about possible predictors of long-term survival on biologic disease-modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission. The clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI-based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan-Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox-regression models. Eight-six patients were on SDAI remission, and the survival rate of bDMARDs since 'baseline-time' was 82.6% (MST=77.8 (95% CI: 69-86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST=86.3 (95% CI: 78-95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST=56.9 (95% CI: 45-69) months; P=.008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST=81.8 (95% CI: 73-91) months) than patients who were not taking MTX (66.7% (MST=55.3 (95% CI: 40-71) months) (log-rank 4.72, P=.03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10-0.93) and methotrexate co-therapy (HR 0.34, 95% CI: 0.12-0.98) were independently associated with a lower risk of bDMARD discontinuation. Among RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD.

Elevated Granulocyte Colony-stimulating Factor Levels in Patients With Active Phase of Adult-onset Still Disease.

Neutrophilia is a hallmark of adult-onset Still disease (AOSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AOSD. Sera were collected from 70 patients with AOSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory variables, and LDG levels in patients with AOSD were analyzed by Spearman correlation test. Patients with active AOSD presented significantly higher levels of G-CSF compared to inactive AOSD patients (P < 0.001) and HCs (P < 0.0001). The G-CSF levels were significantly decreased after active AOSD patients achieved disease remission (P = 0.0015). The G-CSF levels were significantly correlated with C-reactive protein, erythrocyte sedimentation rate, ferritin, and systemic score in AOSD (P < 0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (P < 0.0001), neutrophil-to-lymphocyte ratio (P < 0.0001), percentages of LDGs in the peripheral blood mononuclear cells (P = 0.004), as well as absolute numbers of circulating LDGs (P = 0.018) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy, or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (P < 0.05). Our findings indicate that G-CSF is implicated in the pathogenesis of AOSD, and targeting G-CSF may have therapeutic potential for AOSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

Adherence with methotrexate in polish patients-Survey research results.

Methotrexate (MTX) is the first-line medicine used in most inflammatory joint diseases. It is highly effective but, it's burdened with common side effects and the result of treatment is not immediately visible. This fact significantly increases the risk of unsatisfying patients' compliance. It may lead to difficulties in achieving disease remission and unjustified escalation of treatment. The aim of the study was to evaluate the methotrexate treatment schemes and to assess the patients' compliance with the treatment. The study was based on an online questionnaire distributed to rheumatic patients treated with MTX. The questions about MTX therapy, treatment monitoring, patients' compliance and causing of skipping drug doses were asked. The questionnaire was filled up by 415 patients (21 men, 394 women and average age 36±12.3). In 238 cases the MTX therapy was discontinued, in 148 the decision was taken by the physician, the others discontinued treatment on their own (90 subjects). From the group of patients who stopped taking MTX, 140 returned to the previous treatment. The most common cause of stopping treatment was gastrointestinal (GI) side effects. Self-discontinuation was more often explained by unbearable side-effects (63.33% vs 44.59%; P=.005) such as GI complaints, headaches and bad mood. The doctor's decision to stop treatment was more often caused by the occurrence of liver damage and the improvement of the patient's condition. Good compliance was declared by 346 patients. Most of them (61.69%) admit to skipping MTX doses. The most common reasons for missing a dose were: infectious disease and forgetfulness. The group of patients with good adherence to therapy was significantly older with longer disease duration. High adherence with prescribed MTX is associated with good treatment tolerance, while the occurrence of side effects significantly increases the risk of discontinuation, often without consulting the physician.

Red light-emitting diode treatment improves tissue recovery in DSS-induced colitis in mice

Inflammatory bowel diseases are debilitating illnesses characterized by severe inflammation of the gastrointestinal tract. Treatments currently available are expensive and ineffective. We here investigated the role of red-light emitting diode (LED) on dextran sodium sulfate (DSS)-induced colitis. DSS was added to the drinking water of male mice at days 0, 2, 4 and withdrawn at day 6. LED irradiation was performed daily for 90s from day 6 to 9 on the right and left sides of the ventral surface and beside the external anal region. LED treatment decreased the amount of crypt dysplasia/edema, inflammatory infiltrates and ulcers, attenuated apoptosis and increased proliferation of crypt cells. Also, LED treatment induced expression of annexin A1 in the damaged epithelium, preserved the organization of claudin-1 and skewed cytokine profiling towards a more anti-inflammatory status. Thus, LED treatment promotes structural protection and modulates the inflammatory response, constituting a potential non-invasive and low-cost combined therapy to help patients achieve disease remission.

HL-298: Hodgkin Variant of Richter Transformation: A Case Report

Context Richter Transformation (RT), also known as Richter's syndrome, is defined as the development of an aggressive large-cell lymphoma in the context of underlying chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The incidence of RT ranges from 2 to 9% of all CLL/SLL cases and usually has a poor prognosis with an average survival of five to eight months. Hodgkin lymphoma (HL) is reported to be one of the rarest histological types of RT. Clinically, patients are presented with symptomatic deterioration after achieving disease remission. Due to data scarcity, the recommendations on therapy are limited. The response rate and clinical endpoints are suggested to be slightly inferior compared to in de novo HL but higher than other forms of RT. Objective The objective of this report is to fill the gap in the data and knowledge regarding rare subtype of Richter Transformation and its treatment efficacy. Design This is an ongoing case report with an updating follow-up. Setting This case was evaluated and managed in two independent medical centers: one in Armenia and one in the U.S. Patients or other participants A 67-year-old male with no remarkable previous medical history was diagnosed with CLL/SLL in 2015 and successfully received four cycles of fludarabine and cyclophosphamide as treatment with the elimination of leukocytosis and reduction of adenopathy as a result. After four years in a stable health condition, the patient developed regular fever once a week, as well as right-sided cervical and axillary lymphadenopathy without night sweats, chills, or weight loss. Interventions After a diagnostic workup, including blood tests and CT scans of the chest, neck, and abdomen, as well as a pathohistological examination of a right cervical lymph node biopsy, the diagnosis of Hodgkin variant of RT was established. The decision was made to proceed with the six-course treatment of ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine). The patient is currently under the supervision of specialized medical team care and demonstrates high tolerability to the treatment.

Elevated circulating pro-inflammatory low-density granulocytes in adult-onset Still's disease.

Neutrophilia is a hallmark of adult-onset Still's disease (AOSD). This study aimed to investigate the role of a distinct subset of granulocytes, the low-density granulocytes (LDGs) in the pathogenesis of AOSD. A total of 56 patients with AOSD were included in the study. LDGs were quantified by flow cytometry. Correlations between LDGs with disease activity and laboratory parameters were determined by Spearman's nonparametric test. The cellular sources of the pro-inflammatory cytokines in AOSD were determined by intracellular staining. Active AOSD patients displayed significantly higher levels of LDGs compared with inactive AOSD patients and healthy controls (HCs) (P<0.001). Circulating LDGs were significantly correlated with CRP, ESR and the modified Pouchot score in patients with AOSD (P<0.01). The levels of LDGs were significantly decreased after the active AOSD patients achieved disease remission (P=0.0391). CD14+ monocytes constituted over 90% IL-1β+ peripheral blood mononuclear cells (PBMCs) and over 80% TNF-α+ PBMCs in both active AOSD patients and HCs, respectively. In active AOSD, CD14+ monocytes accounted for 24.6% to 75.0% of IL-6+ PBMCs, while LDGs comprised 22.8% to 72.2% of IL-6+ PBMCs. In contrast, over 90% IL-6+ PBMCs were CD14+ monocytes in HCs. A significant correlation was identified between the levels of LDGs and serum IL-6 levels in AOSD (P<0.0001). Active AOSD is associated with elevated levels of a pro-inflammatory subset of neutrophils, the LDGs that produce IL-6. Our data highlight an unappreciated role of LDGs in the aberrant innate immune responses in AOSD.

Gamma-glutamyl hydrolase gene polymorphisms – another way to predict methotrexate efficacy in rheumatoid arthritis

The current treatment strategy for rheumatoid arthritis has been formulated within the framework of the European League Against Rheumatism (EULAR) concept “Treatment to achieve the goal”. Methotrexate prescribed as soon as possible after verifying rheumatoid arthritis is recognized as a first-line drug that allows to achieve disease remission and prevent destructive changes in the joints. Long-term clinical experience of using methotrexate allowed to conclude that almost 30% patients with rheumatoid arthritis turn out to be resistant to such treatment, enforcing to change the basal anti-inflammatory therapy, shift to using targeted or genetically engineered biological drugs, so that timeframe to prevent disease progression can be irreversibly lost. In the last decade, genetic testing for drug therapy effectiveness has been gaining momentum based on individual features in functioning of enzyme systems which regulate various stages of drug biotransformation. To date, a personalized approach to treatment of rheumatoid arthritis may be implemented after examining more than a dozen of single nucleotide polymorphisms (SNPs) within the folate cycle genes responsible for metabolizing methotrexate as well as its mechanism of action. In our work, we attempted to test a relationship between therapeutic response (efficacy and resistance) to methotrexate and -401CT (rs 3758149) SNP in the GGH (gamma-glutamyl hydrolase) gene, which coordinates the processes of extracellular methotrexate transport. A groups patients consisted of 85 basic anti-inflammatory therapy-naïve patients diagnosed with rheumatoid arthritis, who were initially treated with methotrexate at a dose of 10 to 17.5 mg per week, with subsequently assessed therapeutic efficacy 6 months after the treatment onset based on dynamics in DAS28 index that allowed to identify groups of “responders” and “non-responders”. Next, all patients from select groups underwent molecular genetic typing for GGH-401CT SNP by using real-time polymerase chain reaction. Our study allowed to find that prevalence of the TT homozygous genotype (OR = 5.09; 95% CI 1.11- 23.3; p = 0.037) dominated in “methotrexate non-responders”, whereas “methotrexate responders” tended to have higher C allele frequency (OR = 0.54; 95% CI 0.27-1.01; p = 0.087), which allowed to identify them by genetic predictors of methotrexate therapeutic response in rheumatoid arthritis.

Initial seronegative immune-mediated necrotising myopathy with subsequent anti-HMGCR antibody development and response to rituximab: case report

BackgroundImmune-mediated necrotising myopathy (IMNM) is characterised by severe muscle weakness and necrosis with a paucity of inflammation on muscle biopsy. Around 60% of cases are associated with antibodies to the signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR); the remainder are seronegative. IMNM is more treatment resistant than inflammatory myopathies.Case presentationA 69-year-old woman with previous statin exposure presented aged 63 with muscle weakness and raised creatinine kinase (CK). Anti-SRP and anti-HMGCR antibodies were not detected, but muscle biopsy revealed changes consistent with necrotising myopathy. Statins were discontinued, and she was treated with prednisolone and methotrexate achieving disease remission. Clinical and biochemical parameters were largely stable until 6 years after diagnosis she experienced a rapid deterioration. This was found to be associated with new development of anti-HMGCR antibody. Rituximab was commenced, resulting rapidly in remission. She has remained in remission since, following 2 cycles of rituximab.ConclusionsTo our knowledge, this is the first reported case of serologically negative IMNM whose subsequent rapid deterioration was associated with development of anti-HMGCR antibody. The response to rituximab and subsequent sustained remission suggests a role for early use of rituximab in aggressive cases of anti-HMGCR myopathy.

Dapsone in the Management of Pemphigus and Pemphigoid: Rediscovery of its Long-Lost Efficacy.

IntroductionAutoimmune mucocutaneous blistering dermatoses (AMCBD) are a group of disorders characterized by the production of autoantibodies that target specific adhesion molecules of the skin and/or mucous membranes. As a result, there is blister formation on the skin with or without mucous membrane involvement. Systemic corticosteroids have been used as the mainstay of treatment in AMCBD. However, due to the debilitating side effects associated with their use, there is significant morbidity and mortality, especially on the fragile elderly patients. Although the efficacy of dapsone in the treatment of AMCBD was identified decades ago, few recent studies shed light on that. Hence, further studies are needed to evaluate the efficacy of dapsone as a single agent in maintaining disease remission in patients with AMCBD.Materials and methodsAn observational retrospective study was performed. Patients with a known diagnosis of bullous pemphigoid (BP) or pemphigus vulgaris (PV) who are treated with dapsone with or without low-dose systemic corticosteroids were included in the study, and their medical files were reviewed. ResultsA total of seven patients were included (three males and four females). All patients showed a satisfactory response to dapsone, achieving disease remission in a short period of time with no serious side effects necessitating treatment cessation.ConclusionsOur findings support that dapsone may have a corticosteroid-sparing effect in the management of AMCBD. Further studies are warranted to confirm our findings.

OP0011 A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED STUDY OF AVACOPAN IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS

Background:Complement fragment C5a is strongly linked to the pathogenesis of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV). C5a receptor (C5aR), present on neutrophils, is a G protein-coupled receptor for C5a. Avacopan (previously CCX168) is an orally-administered selective antagonist of C5aR which blocks C5a-induced cell activation. Two previous Phase 2 clinical trials provided evidence of effectiveness of avacopan in AAV and its potential to eliminate extensive use of glucocorticoids (GC) and GC-related toxicities.Objectives:This Phase 3 study evaluated the efficacy and safety of avacopan for the treatment of AAV.Methods:Eligible subjects were randomized 1:1 to receive either prednisone or avacopan in combination with either a) cyclophosphamide (oral or IV) followed by azathioprine or b) rituximab (four IV infusions). Randomization was stratified by the treatment regimen (rituximab, IV cyclophosphamide, or oral cyclophosphamide), ANCA serotype, and newly-diagnosed or relapsing disease. Treatment period was 52 weeks; primary efficacy endpoints were the proportion of subjects achieving disease remission at Week 26, and sustained disease remission at Week 52. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of zero and not taking glucocorticoids for AAV within 4 weeks prior to Week 26. Sustained remission was defined as being in remission at Week 26 and also subsequently in remission as defined above at Week 52. Any relapse of AAV between Weeks 26 and 52 was considered not achieving sustained remission.Results:330 subjects were randomized and dosed: 166 in avacopan and 164 in prednisone arms. At Week 26, 72.3% subjects achieved remission in the avacopan arm compared to 70.1% in the prednisone arm (p&lt;0.0001 for non-inferiority). At Week 52, 65.7% subjects achieved sustained remission in the avacopan arm compared to 54.9% in the prednisone arm achieving both non-inferiority and superiority to prednisone arm (p=0.0066 for superiority of avacopan).The avacopan arm had a significant reduction in glucocorticoid-related toxicity compared to the prednisone arm as measured by the Glucocorticoid Toxicity Index (GTI) of Cumulative Worsening Score (p=0.0002) and Aggregate Improvement Score (p=0.0082).In subjects with renal disease at baseline, the avacopan arm showed a mean increase in estimated glomerular filtration rate (eGFR) of 7.3 mL/min/1.73 m2 from baseline to week 52 as compared to 4.0 mL/min/1.73 m2 increase in the prednisone arm (p=0.0259).Overall subject incidence of serious adverse events (SAEs) was generally consistent with previous AAV trials at 45.1% and 42.2% for prednisone and avacopan groups, respectively. Serious infections were 15.2% and 13.3%, serious hepatic adverse events 3.7% vs 5.4%, and SAEs of white blood cell count decreases were 4.9% vs 2.4% for prednisone and avacopan, respectively. No meningococcal infections were reported.Conclusion:Avacopan treatment resulted in remission in AAV patients receiving rituximab or cyclophosphamide/azathioprine at a rate that was non-inferior to the active comparator prednisone at week 26 and superior to prednisone in sustained remission at Week 52. A significant reduction in glucocorticoid-related toxicity was observed in the avacopan vs. prednisone arms. Significant increase in eGFR in subjects with renal disease was also observed in avacopan vs. prednisone. The safety profile of avacopan appears acceptable for development in AAV. Avacopan treatment for AAV is efficacious and exhibits benefits not seen with chronic prednisone therapy.

1047-P: The Change of HOMA-IR Predicted the Remission Time in Patients with Newly Diagnosed Type 2 Diabetes after Intensive Insulin Therapy

Objectives: Insulin resistance is one of strong predictions on the remission in patients with newly diagnosed type 2 diabetes (T2DM) after short-term insulin intensive therapy (SIIT). Therefore, the purpose of this study is to explore if the short-term change of insulin resistance can predict the long-time remission. Methods: This study enrolled 160 patients with newly diagnosed type 2 diabetes mellitus (103 male, aged 49.8±10.4 yrs,HbA1c11±2.1%). All of them have been treated by 2-week continuous subcutaneous insulin infusion as SIIT when new diagnosed. HOMA-IR was compared just at the termination of SIIT and later then follow up every 3 months regularly for 5 years. Results: After short-term intensive treatment, up to 84.4%, 81.3% and 26.9% of patients achieved disease remission with T2DM at the termination of CSII, the 3rd month and 5th year follow up without use of medication. The average remission time were 27+/-615 months. The average changes of HOMA-IR in the first 3 months after SIIT were 30%+/-52%. This short-term change percent of HOMA-IR was positive related to the statue of remission at 5th-year follow-up (r = 0.778, p &amp;lt;0.0001). The ROC curve analysis showed below. Conclusions: Maintaining the improving insulin resistance after short-term insulin intensive therapy is essential for the long-time remission from T2DM. Lifestyle interventions might be helpful. Disclosure W. Xuesi: None. Z. Huang: None. L. Liu: None. Y. Li: None. Funding National Key Research and Development Program of China (2018YFC1314100)

LB003A RANDOMIZED, DOUBLE-BLIND, ACTIVE CONTROLLED STUDY OF AVACOPAN IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS

Abstract Background and Aims Complement fragment C5a is strongly linked to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The C5a receptor (C5aR), is a G protein-coupled receptor present on neutrophils. Avacopan (previously CCX168) is an orally-administered selective antagonist of C5aR which blocks C5a-induced cell activation. Two previous Phase 2 clinical trials provided evidence of effectiveness of avacopan in AAV. This Phase 3 study evaluated the efficacy and safety of avacopan for the treatment of AAV as well as the potential of avacopan to eliminate extensive use of glucocorticoids (GC) and GC-related toxicities. Method Eligible subjects were randomized 1:1 to receive either prednisone or avacopan in combination with either a) cyclophosphamide (oral or IV) followed by azathioprine or b) rituximab (four IV infusions). Randomization was stratified by the treatment regimen (rituximab, IV cyclophosphamide, or oral cyclophosphamide), ANCA serotype, and newly-diagnosed or relapsing disease. Treatment period was 52 weeks; primary efficacy endpoints were the proportion of subjects achieving disease remission at Week 26, and sustained disease remission at Week 52. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS) of zero and not taking glucocorticoids for AAV within 4 weeks prior to Week 26. Sustained remission was defined as being in remission at Week 26 and sustained through Week 52 without relapse. Change in estimated glomerular filtration rate (eGFR) from baseline to week 52 was a pre-specified secondary endpoint. Results 330 subjects were randomized and dosed: 166 in the avacopan and 164 in the prednisone groups. At Week 26, 72.3% subjects achieved remission in the avacopan compared to 70.1% in the prednisone group (p&amp;lt;0.0001 for non-inferiority). At Week 52, 65.7% subjects achieved sustained remission in the avacopan compared to 54.9% in the prednisone group achieving both non-inferiority and superiority to prednisone group (p=0.0066 for superiority of avacopan). The avacopan arm had a significant reduction in glucocorticoid-related toxicity compared to the prednisone arm as measured by the Glucocorticoid Toxicity Index of Cumulative Worsening Score (p=0.0002) and Aggregate Improvement Score (p=0.0082). In subjects with renal disease at baseline, the avacopan group (n=134) showed a mean increase in eGFR of 7.3 mL/min/1.73 m2 from baseline to week 52 as compared to 4.1 mL/min/1.73 m2 increase in the prednisone group (n=132) (p=0.029). A pre-specified sub-group analysis showed a greater difference in the avacopan sub-group with a baseline eGFR &amp;lt;30 (13.7 mL/min/1.73 m2 vs. 8.2 mL/min/1.73 m2; p&amp;lt;.005). Conclusion Treatment with avacopan resulted in remission in patients with AAV receiving rituximab or cyclophosphamide/azathioprine at a rate that was non-inferior to the active comparator prednisone at Week 26 and superior to prednisone in sustained remission at Week 52. A significant reduction in glucocorticoid-related toxicity was observed in the avacopan vs. prednisone arms. The increase in eGFR seen with avacopan was marked among subjects with more severe renal disease. The safety profile of avacopan was acceptable for use in patients with AAV. The ADVOCATE trial demonstrated avacopan is an effective treatment for patients with AAV.

Peficitinib for the treatment of rheumatoid arthritis: an overview from clinical trials

ABSTRACT Introduction The treatment of rheumatoid arthritis (RA), a chronic, systemic, autoimmune disease, has been greatly advanced by the introduction of biologic disease-modifying antirheumatic drugs (DMARDs); however, many patients still fail to achieve disease remission. Peficitinib, an orally bioavailable inhibitor of the Janus kinase (JAK) receptor family, was approved in Japan in 2019 and Korea in 2020 for the treatment of RA. Areas covered This review provides an overview of JAK inhibitors currently marketed or in development; the pharmacodynamics and pharmacokinetics of peficitinib; and the efficacy and safety data for peficitinib from Phase 2b and 3 trials. Expert opinion Peficitinib has proven clinical efficacy in Asian patients (Japan, Korea, and Taiwan) with RA who have an inadequate response to conventional DMARDs. In Phase 3 trials, clinical improvements and prevention of joint destruction were demonstrated for both 100 mg and 150 mg once-daily peficitinib versus placebo, and treatment for up to 52 weeks was well tolerated. Safety signals, in particular the increased incidence of herpes zoster-related disease, appeared in line with other JAK inhibitors. Post-launch monitoring will establish the long-term safety and effectiveness of this drug, and further studies are necessary to determine its potential use in non-Asian populations.

Evaluation of the Effectiveness and Tolerability of Mycophenolate Mofetil and Mycophenolic Acid for the Treatment of Morphea

First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak. To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.

Cannabis in inflammatory bowel disease: a narrative summary

Introduction: Although cannabinoids have been used for several years, only recently have their mechanisms of action and therapeutic targets been described. Alterations in the endocannabinoid system have been observed in various diseases and conditions such as pain, inflammation, autoimmune diseases and various specific disorders. Inflammatory bowel disease groups two chronic idiopathic conditions with uncertain pathogeneses in which deregulation of the immune system plays an important role. Alternative treatments need to be developed for these patients since only a minority of patients achieve disease remission. Our goal is to review recent evidence related to the use of cannabis to treat ulcerative colitis and Crohn’s disease.&#x0D; Methods: This is a focused narrative review based on searches of Pubmed and Embase. Relevant articles have been reviewed and summarized in narrative form.&#x0D; Results: The two main components of cannabis, CBD and THC, have been extensively studied, and their anti-inflammatory and antinociceptive effects have been tested. The effects of these components for control of the symptoms of ulcerative colitis and Crohn’s disease have been widely described. However, high quality studies are needed to continue evaluating the efficacy and safety of cannabis use in patients with inflammatory bowel disease.

P169 DEFINITION OF REMISSION IN INFLAMMATORY BOWEL DISEASE: ASSESSMENT OF PATIENT AND PHYSICIAN PERSPECTIVES

A primary goal in IBD management is achieving disease remission; however, patient (pt)-physician alignment on this goal is unclear. International online surveys were conducted to gain insights into pts’ and physicians’ perspectives on real-world management of IBD. Herein, we report survey findings pertaining to their understanding and perceptions of disease remission in IBD.

P169 DEFINITION OF REMISSION IN INFLAMMATORY BOWEL DISEASE: ASSESSMENT OF PATIENT AND PHYSICIAN PERSPECTIVES

Abstract Background A primary goal in IBD management is achieving disease remission; however, patient (pt)-physician alignment on this goal is unclear. International online surveys were conducted to gain insights into pts’ and physicians’ perspectives on real-world management of IBD. Herein, we report survey findings pertaining to their understanding and perceptions of disease remission in IBD. Methods Surveys were completed online by pts and physicians in Canada, France, Germany, Italy, Spain, UK, and US. Using a mixed-recruitment method, pts were identified by physicians, pt advocacy groups, and panels, while physicians were identified by recruitment agencies and panels. Eligible pts were aged ≥18 y who were diagnosed with and received treatment for Crohn’s disease (CD) or ulcerative colitis (UC) and had not undergone surgery for UC. Eligible physicians were gastroenterologists who had treated pts with CD or UC (≥12 each) in the last month, were responsible for treatment decisions of their IBD pts, and for whom ≥30% of their IBD pts had moderate or severe disease per prespecified clinical criteria. A 1:1 CD:UC ratio was targeted for the pt survey. Alignment between pts and physicians on remission definitions and pt-physician communication about remission was assessed. Physicians’ estimates of remission rates in their moderate/severe IBD pts receiving biologic therapy and their satisfaction (1=very dissatisfied to 7=very satisfied) with remission rates with current IBD treatments also were reported. Results A total of 2398 IBD pts (1368 CD [40% male], 1030 UC [45% male]) and 654 physicians completed the surveys. Mean pt age was 42 y (CD) and 44 y (UC). Physicians had mean monthly caseloads of 42.9 (CD) and 43.3 (UC). The most common primary care settings were university/teaching hospitals (41%), private practices (31%), and regional/community hospitals (20%). Nearly one quarter of pts reported never having discussed remission with their physician; only 7% of physicians reported that they typically did not discuss remission with their pts. Pts most commonly defined remission as symptom resolution (45%), whereas most physicians defined remission through test results (64% CD, 70% UC), including colonoscopies (56% CD, 58% UC), biopsies (36%, 37%), and biochemical tests (8%, 6%). Most pts (62% CD, 64% UC) had never heard of the term “mucosal healing.” Despite low physician-reported remission rates (CD: 37%–54%; UC: 37%–55%), 25% and 36% of physicians reported high satisfaction (score ≥6) with CD and UC remission rates, respectively. Conclusions This international survey demonstrated differences in pts’ and physicians’ definitions of IBD remission and in their understanding of the role of histologic remission in IBD. The findings highlight the need for improved pt-physician communication and education regarding remission, which may improve adherence and outcomes.

Management of ankylosing spondylitis; present concepts and guidelines

Ankylosing spondylitis (AS) belongs to spondyloarthritis (SpA) group of inflammatory arthritis, which has common genetic, clinical, and radiological features. The management aims at improving the quality of life, long-term control of inflammation so as to prevent structural damage, preserve functional abilities, and maintain the social life of patients. Treatment strategies and modalities in inflammatory arthritis have tremendously improved in recent times. With the discovery of molecular mechanisms, a new series of targets involving the cytokines, cells, and intracellular signaling pathways have been explored. The introduction of tumor necrosis factor inhibitor drugs heralded a new era of therapeutics for SpA, especially AS. Recently, the licensing of secukinumab, an interleukin 17A inhibitor for the treatment of AS, has given a new pathway to look at. These new targets give us an opportunity to achieve disease remission in both AS and nonradiologic axial SpA. They have also opened up new horizon to look for different research strategies in achieving disease remission using biological drugs in early disease and in stratified manner. International societies have been regularly providing and updating the guidelines for the management of AS. In this review, we discuss the treatment of AS and future trends in the management.

Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing.

Rheumatoid arthritis is a chronic, systemic joint disease in which an autoimmune response translates into an inflammatory attack resulting in joint damage, disability and decreased quality of life. Despite recent introduction of therapeutic agents such as anti-TNFα, even the best current therapies fail to achieve disease remission in most arthritis patients. Therefore, research into the mechanisms governing the destructive inflammatory process in rheumatoid arthritis is of great importance and may reveal novel strategies for the therapeutic interventions. To gain deeper insight into its pathogensis, we have developed for the first time a three-dimensional synovium-on-a-chip system in order to monitor the onset and progression of inflammatory synovial tissue responses. In our study, patient-derived primary synovial organoids are cultivated on a single chip platform containing embedded organic-photodetector arrays for over a week in the absence and presence of tumor-necrosis-factor. Using a label-free and non-invasive optical light-scatter biosensing strategy inflammation-induced 3D tissue-level architectural changes were already detected after two days. We demonstrate that the integration of complex human synovial organ cultures in a lab-on-a-chip provides reproducible and reliable information on how systemic stress factors affect synovial tissue architectures.