Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt–Koyanagi–Harada Disease

This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt–Koyanagi–Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt–Koyanagi–Harada disease may achieve better control with adalimumab and methotrexate combination therapy.

Unconventional treatment options in psoriasis: A review

Psoriasis is a common skin disease that affects 1–3% of the general population. The treatment depends on body surface area involved, quality of life impairment and associated comorbidities. The treatment options include topical therapy, phototherapy, conventional systemic therapy (methotrexate, cyclosporine and acitretin), biologics and oral small molecules (apremilast and tofacitinib). Despite the availability of newer therapies such as biologics and oral small molecules, many a time, there is a paucity of treatment options due to the chronic nature of the disease, end-organ toxicity of the conventional drugs or high cost of newer drugs. In these scenarios, unconventional treatment options may be utilized as stand-alone or adjuvant therapy. In this review, we have discussed these uncommonly used treatment options in the management of psoriasis.

The maximum dose and duration in the therapy single use methotrexate to achieve remission by rheumatoid arthritis patients through disease activity score 28 (DAS28)

Objectives One of the treatments for rheumatoid arthritis (RA) was methotrexate which a disease modifying antirheumatic drug therapy. The use of methotrexate required the right dose and length of therapy to achieve remission. The effectivity of methotrexate could be accounted by disease activity score 28 (DAS28) as a tool has been used clinically with a combination number of tender joints, swollen joints, erythrocyte sedimentation rate, and global clinical assessment by the patient. The aim of this study was to determine the effective dose and length of therapy methotrexate was measured by DAS28 score. Methods This research was a cross-sectional study and data was collected from patient medical records in Saiful Anwar Hospital, Malang, from February to July 2018. The research has been given ethical clearance. The inclusion criteria for the 88 subjects were men and women, over 20 years of age, usage of only methotrexate for at least three months, an erythrocyte sedimentation rate score, uncomplicated inflammatory bowel disease, cancer, and systemic lupus erythematosus. All data obtained was entered in formula DAS28. The Statistic analysis used both Pearson and Spearman’s rank correlation. Results Only 16 patients achieved remission. There were not significant correlation in statistical analysis between DAS score and cumulative dose (r=−0.091; p=0.400), average dose (r=0.043; p = 0.692), maximum dose (r=0.074; p=0.492), and length of therapy (r=−0.075; p = 0.489). The initial dose of therapy methotrexate was different and the length of therapy was adjusted to the patient’s health condition. Conclusions The maximum dose and length of therapy methotrexate was required to achieve remission in RA.

Febbre di origine sconosciuta (FUO): approccio diagnostico attraverso un caso clinico

The paper reports the case of a 12-year-old female affected by ulcerative colitis and treated with double immunosuppressant therapy (methotrexate and infliximab). The patient presented with 7 day-lasting fever associated with pharyngotonsillar hyperaemia, cheilitis, vesicular-bollous lesions on labial mucosa and rash on malar regions, chest and upper extremities. Since full blood count showed lymphocytosis and inflammatory markers were negative, a viral infection was suspected. Virological tests identified the presence of IgM against Cytomegalovirus (CMV), Herpes and Mumps viruses, but Real-Time PCR was negative for the DNA detection of any of those viruses. Despite hospital admission and different investigations, fever persisted for more than 7 days without any explanation. Therefore, it was considered as Fever of unknown origin (FUO). FUO is often an unusual manifestation of a common disease but so far there is not a single validated diagnostic protocol. In the presented case only did the repetition of the Real-Time PCR test after a few days enable CMV DNA to be identified in the patient’s blood and urine and CMV infection to be diagnosed.

Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in Model Arthritis

Chronic inflammatory autoimmune disorders are systemic diseases with increasing incidence and still lack a cure. More recently, attention has been placed in understanding gastrointestinal (GI) dysbiosis and, although important progress has been made in this area, it is currently unclear to what extent microbiome manipulation can be used in the treatment of autoimmune disorders. Via the use of appropriate models, rheumatoid arthritis (RA), a well-known exemplar of such pathologies, can be exploited to shed light on the currently overlooked effects of existing therapies on the GI microbiome. In this direction, we here explore the crosstalk between the GI microbiome and the host immunity in model arthritis (collagen induced arthritis, CIA). By exploiting omics from samples of limited invasiveness (blood and stools), we assess the host-microbiome responses to standard therapy (methotrexate, MTX) combined with mechanical subcutaneous stimulation (MS) and to mechanical stimulation alone. When MS is involved, results reveal the sphingolipid metabolism as the trait d’union among known hallmarks of (model) RA, namely: Imbalance in the S1P-S1PR1 axis, expansion of Prevotella sp., and invariant Natural Killer T (iNKT)-penia, thus offering the base of a rationale to mechanically modulate this pathway as a therapeutic target in RA.

A case of myositis with immunological background associated with statin use

Statins might cause and/or aggravate the immune-mediated myositis in patients on long-term, stable treatment. We provide a case of polymyositis with an immunological background and gastrointestinal and urinary manifestations in patient on long-term, stable atorvastatin treatment for the past six years. The diagnose of polymyositis was established based on clinical symptoms and signs, electromyography and laboratory test results (elevated aspartate aminotransferase 279 U/L, reference range 0–40 U/L; alanine aminotransferase 198 U/L, 0–33 U/L; lactate dehydrogenase 2200 U/L, 103-227 U/L; creatine kinase 7820 U/L, 15–84 U/L; and positive antinuclear antibodies test, titer of 1:160, with suspect antisynthetase antibodies). Polymyositis was probably related to atorvastatin treatment (Naranjo score, 5). Other probable causes of the myositis were rejected. Coricosteroid therapy, methotrexate and supplementation with vitamin D did not improve the condition. The patient remained bedridden and died two months after the hospital discharge due to the acute myocardial infarction.

Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial

BackgroundRecently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA).ObjectiveTo assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept.MethodsAn open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39.ResultsBoth groups showed major improvements in DAS44 after 52 weeks: mean (SD) −2.41 (1.2) in the COBRA and −2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it.ConclusionsIntensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation.Trial registration number:ISRCTN55552928.