piperidines and Dermatomyositis

Topics: Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Piperidines; Pyrimidines

JDM is a rare autoimmune inflammatory muscle disease with a pronounced IFN signature. Treatment for children with JDM has improved over the years with the use of steroids and immunosuppressive agents. However, there remains a subset of children who have refractory disease. Janus kinase and type I IFN signalling production are suspected to contribute to the pathogenesis of JDM. Our pilot study investigated the use of tofacitinib, a Janus kinase inhibitor, in refractory JDM cases to provide new therapeutic options for better treatment.. Refractory JDM was defined as patients who failed two or more steroid sparing agents or high-dose steroids. Tofacitinib was given to three refractory JDM patients with a dose of 5 mg twice per day for at least 6 months. Core set measures defined by Pediatric Rheumatology International Trials Organization were evaluated at month 0, 3 and 6 along with other systemic evaluations. A literature review was conducted to identify all the cases using Janus kinase inhibitors in JDM.. All three subjects tolerated and responded well to tofacitinib with significant improvement in Child Myositis Assessment Scale, manual muscle testing-8, physician global disease activity and inflammatory indices without occurrence of severe adverse events.. This pilot study showed improvement of muscle strength, resolution of cutaneous lesions, increased daily quality of life and successful tapering of steroids when tofacitinib used in selected cases. Tofacitinib can be considered with caution when treating refractory JDM cases. Further randomized controlled trials are warranted to assess its efficacy in JDM.

Topics: Child; Creatine Kinase; Dermatomyositis; Female; Glucocorticoids; Humans; Janus Kinase Inhibitors; Lung Volume Measurements; Male; Muscle Strength; Pilot Projects; Piperidines; Pyrimidines

Interstitial lung diseases (ILDs) have been reported to be associated with myositis (including polymyositis and dermatomyositis). These myositis-associated ILDs carry significant morbidity and mortality. This review summarizes recent findings on myositis-associated ILD with a focus on pathogenesis and emerging treatment.. Recent advances in genetics have revealed 22 myositis-associated genome-wide loci, which were significantly enriched in regulatory regions in immune cells. An analysis of such disease-associated loci elucidated potential drug targets (e.g., TYK2 targeted by tofacitinib). In another study, an intronic variant in WDFY4 in association with clinically amyopathic dermatomyositis (CADM) had an effect for higher expression of a truncated WDFY4 isoform. Truncated WDFY4 markedly enhanced the MDA5-mediated NF-κB activation and cell apoptosis, indicating the dysregulated WDFY4-MDA5 pathway as a novel pathogenesis of CADM. As a novel strategy, tofacitinib treatment showed a promising improvement in survival and clinical features of CADM-associated ILD.. The genetic differences in the myositis-susceptible loci may explain the heterogeneous phenotypes and treatment responses in myositis-associated ILD. The understanding of pathogenesis with the genetic background as well as autoantibodies will enable the practice of personalized treatment in the management of the disease.

Topics: Apoptosis; Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Intracellular Signaling Peptides and Proteins; Lung Diseases, Interstitial; Molecular Targeted Therapy; Myositis; NF-kappa B; Phenotype; Piperidines; Polymyositis; Pyrimidines; Signal Transduction; TYK2 Kinase

We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets.. An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry.. Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline.. Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.

Topics: Adult; Aged; Dermatomyositis; Female; Glucocorticoids; Humans; Janus Kinase Inhibitors; Male; Middle Aged; Piperidines; Prospective Studies; Pyrimidines; Treatment Outcome

Topics: Adult; Autoantibodies; Dermatomyositis; Drug Therapy, Combination; Female; Glucocorticoids; Historically Controlled Study; Humans; Interferon-Induced Helicase, IFIH1; Janus Kinase Inhibitors; Lung Diseases, Interstitial; Male; Methylprednisolone; Middle Aged; Piperidines; Pyrimidines; Pyrroles

Topics: Autoantibodies; Calcinosis; Dermatomyositis; Humans; Interferons; Piperidines

Topics: Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Piperidines; Prognosis; Pyrimidines; Retrospective Studies

This study aimed to evaluate the efficacy and safety of tofacitinib for the treatment of anti-melanoma differentiation-associated 5 gene (anti-MDA5) antibody-positive dermatomyositis (DM).. This study included 52 patients with anti-MDA5 antibody-positive DM (MDA5 + DM) who were treated with tofacitinib and followed up. Clinical and laboratory data of these patients were recorded between January 2019 and June 2022. SPSS was used for all statistical analyses.. The mean age of patients with MDA5 + DM was 45 ± 12.4 years, and the median disease duration was 6.5 months (range, 3-13 months). The mean dosage of glucocorticoids was 34.7 ± 20.9 mg/d at the initiation of tofacitinib therapy. Overall, 47 patients were followed up for a mean duration of 7.8 ± 6.2 months. We found that the clinical symptoms of 28 patients (59.6%) were improved, but 1 patient (2.1%) died because of severe infection. Moreover, complications occurred in 25 patients (53.2%), among whom 19 patients had infections. Older age and C-reactive protein levels close to the upper value in reference range at the initial treatment were found to be the potential risk factors of infection. Furthermore, patients with cutaneous ulcers were found to have a lower risk of infection.. Tofacitinib can be used as a potential therapeutic option for MDA5 + DM. The occurrence of infection requires special attention during treatment, particularly in patients with older age and C-reactive protein levels close to the upper value in reference range.

Topics: Autoantibodies; C-Reactive Protein; Dermatomyositis; Humans; Infant; Interferon-Induced Helicase, IFIH1; Melanoma; Piperidines; Retrospective Studies

Tofacitinib has an important role in pediatric rapidly progressive interstitial lung disease (ILD) associated with juvenile dermatomyositis (JDM), an otherwise potentially fatal condition. It may be useful in induction of remission and can be used safely to maintain remission. Serum ferritin and interleukin-18 are useful markers for tracking activity and response of JDM-associated ILD.

Topics: Child; Dermatomyositis; Humans; Janus Kinase Inhibitors; Lung Diseases, Interstitial; Male; Piperidines; Pyrimidines; Remission Induction

Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: (1) cytokines that were not suppressed by TOF played an important role in RP-ILD; (2) TOF was administered later than previously reported; and (3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.

Topics: Autoantibodies; Cytokines; Dermatomyositis; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Piperidines; Plasma Exchange; Pyrimidines

Dermatomyositis (DM) and alopecia areata are two diseases characterised by aberrant interferon signalling. While patchy alopecia of the scalp is a known feature of DM, alopecia universalis, which involves hair loss over the entire body, has rarely been reported in conjunction with DM. Herein, we report the case of a 30-year-old female with DM who developed refractory cutaneous disease and alopecia universalis that were successfully treated with tofacitinib. This could suggest that concomitant severe alopecia and refractory cutaneous DM may reflect a strong baseline interferon gene signature that may predict responsiveness to janus kinase inhibitors.

Topics: Adult; Alopecia; Alopecia Areata; Dermatomyositis; Female; Humans; Interferons; Piperidines; Pyrimidines; Pyrroles

Dermatomyositis is a rare idiopathic inflammatory disease with diverse presentations that can have varying degrees of cutaneous and systemic involvement. This phenotypic heterogeneity makes DM a therapeutic challenge. Some therapeutic drugs, such as hormones and immunosuppressants, have poor therapeutic effects. In recent years, tofacitinib has been reported to be effective in the treatment of dermatomyositis.. We report a case of anti-MDA5 antibody-positive dermatomyositis that was relieved after treatment with tofacitinib, during which gallbladder gangrene and suppurative cholecystitis occurred. After cholecystectomy, we continued to use tofacitinib and achieved a good therapeutic effect.. Tofacitinib is effective in the treatment of anti-MDA5 antibody-positive dermatomyositis, but the risk of infection is increased. It can still be used after infection control. Close follow-up should be performed during the use of tofacitinib.

Topics: Autoantibodies; Cholecystitis; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Piperidines; Pyrimidines

Dermatomyositis (DM) is an autoimmune myopathy with characteristic dermatologic features.1 Tofacitinib is an immunomodulator with proven efficacy against numerous immune-mediated disorders, including rheumatoid arthritis (RA) and psoriasis.2 Several reports have demonstrated oral tofacitinib’s ability to treat the cutaneous and extracutaneous manifestations of refractory dermatomyositis (DM).1,4,5 However, evidence for sustained improvement remains limited.2,3 The goal of this study is to investigate the long-term response of recalcitrant DM to oral and topical tofacitinib at varied dosing regimens.

Topics: Dermatomyositis; Humans; Immunologic Factors; Piperidines; Pyrimidines; Pyrroles; Retrospective Studies; Treatment Outcome

Topics: Dermatomyositis; Humans; Piperidines; Pyrimidines

Topics: Academic Medical Centers; Dermatomyositis; Humans; Piperidines; Pyrimidines; Retrospective Studies

Topics: Dermatomyositis; Humans; Piperidines; Prospective Studies; Pyrimidines; Time Factors

Anti-melanoma differentiation-associated protein 5 (MDA5)-positive rapidly progressive interstitial lung disease (RP-ILD) is associated with poor prognosis, and the most effective therapeutic intervention has not been established. Herein we report a case of a 45-year-old female patient who presented with myalgia, Gottron's papules with ulceration, and dyspnea on exertion which became aggravated within weeks. Laboratory examination and electromyography confirmed myopathy changes, and a survey of myositis-specific antibodies was strongly positive for anti-MDA5 antibody. High-resolution chest tomography suggested organizing pneumonia with rapidly progressive changes within the first month after diagnosis of the disease. Anti-MDA5-associated dermatomyositis with RP-ILD was diagnosed. Following combination therapy with rituximab, tofacitinib and pirfenidone, clinical symptoms, including cutaneous manifestation, respiratory conditions and radiographic changes, showed significant and sustainable improvement. To our knowledge, this is the first reported case of anti-MDA5-associated dermatomyositis with RP-ILD successfully treated with the combination of rituximab, tofacitinib, and pirfenidone.

Topics: Autoantibodies; Dermatomyositis; Female; Humans; Lung Diseases, Interstitial; Middle Aged; Piperidines; Pyridones; Pyrimidines; Rituximab

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibodies have widely known to be associated with amyopathic dermatomyositis with rapidly progressive interstitial lung disease (ILD). Although the triple combination therapy with high-dose glucocorticoids, cyclophosphamide, and a calcineurin inhibitor has been used to treat anti-MDA-5 antibody-positive rapidly progressive ILD, the prognosis of these patients remains poor despite this intensive therapy. Recently, several investigators have shown that combination therapy with tofacitinib might be potentially efficacious in those patients. We herein report a case of anti-MDA-5 antibody-positive dermatomyositis and associated ILD who had not responded to the triple therapy and tofacitinib 10 mg/day but markedly responded after increasing the dose of tofacitinib to 20 mg/day.

Topics: Autoantibodies; Dermatomyositis; Dose-Response Relationship, Drug; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Middle Aged; Piperidines; Pyrimidines; Recurrence; Treatment Outcome

Topics: Autoantibodies; Dermatomyositis; Humans; Piperidines; Pyrimidines; Pyrroles

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed

Topics: Adenosine Monophosphate; Alanine; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antiviral Agents; Autoantibodies; Bronchoscopy; Child; COVID-19; COVID-19 Nucleic Acid Testing; Cyclophosphamide; Dermatomyositis; Disease Progression; Fatal Outcome; Female; Humans; Hydroxychloroquine; Immunocompromised Host; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Interferon-Induced Helicase, IFIH1; Lung; Lung Diseases, Interstitial; Lymphohistiocytosis, Hemophagocytic; Mediastinal Emphysema; Methylprednisolone; Piperidines; Pneumonia, Pneumocystis; Pneumothorax; Pyrimidines; Respiratory Insufficiency; Shock, Septic; Subcutaneous Emphysema; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Dermatomyositis; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Piperidines; Pyrimidines

This open-label 12-week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment-refractory active dermatomyositis (DM).. Tofacitinib in extended-release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid-sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety.. At 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin.. This is the first prospective, open-label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan-JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.

Topics: Adult; Chemokine CXCL10; Chemokine CXCL9; Dermatomyositis; Female; Humans; Immunohistochemistry; Janus Kinase Inhibitors; Male; Middle Aged; Muscle, Skeletal; Pilot Projects; Piperidines; Proof of Concept Study; Prospective Studies; Pyrimidines; RNA-Seq; Skin; STAT1 Transcription Factor; Treatment Outcome

Topics: Adenosine Triphosphatases; Adult; Antirheumatic Agents; Autoantibodies; Calcinosis; Dermatomyositis; Diffusion Magnetic Resonance Imaging; DNA-Binding Proteins; Female; Humans; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Radiography; Severity of Illness Index; Skin; Treatment Outcome

Topics: Adult; Autoantibodies; Dermatomyositis; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Male; Mediastinal Emphysema; Piperidines; Pyrimidines

Topics: Autoantibodies; Dermatomyositis; Female; Humans; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines

Topics: Calcinosis; Child; Dermatomyositis; Female; Humans; Male; Piperidines; Pyrimidines

Antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive clinically amyopathic dermatomyositis (cADM) is frequently complicated with interstitial lung disease (ILD) and has a poor prognosis. Although the short-term prognosis of anti-MDA5 Ab-positive cADM is poor, it has been suggested that the recurrence rate is not higher than that of anti-MDA5 Ab-negative dermatomyositis. Combination therapy with corticosteroids, calcineurin inhibitors, and cyclophosphamide is the gold standard for the remission induction therapy at the onset. Recently, it has been reported that tofacitinib (TOF) could be effective for refractory anti-MDA5 Ab-positive cADM with ILD. Although initial remission induction therapy has been established, therapeutic strategies for relapse cases have not yet been established.. A 57-year-old woman who was diagnosed with anti-MDA5 Ab-positive cADM complicated with ILD. In October 2016, she was treated with prednisolone (PSL), tacrolimus (TAC), and cyclophosphamide (CY). These treatments were successful, and PSL could be tapered. However, she developed strong nausea and general fatigue as adverse events of CY. In April 2018, PSL was discontinued, and maintenance therapy was given with TAC. In July 2018, Gottron's sign and ILD recurred. Skin lesions on the finger were partially ulcerated and ILD was also worsening. We proposed a remission reinduction therapy including CY. However, she was rejected CY from experience with past adverse event of CY.. Based on skin lesions and chest computed tomography (CT) findings, the diagnosis was a recurrence of anti-MDA5 Ab-positive cADM with ILD.. Treatment by TOF 10 mg and PSL 22.5 mg (0.5 mg/kg equivalent) was introduced in November 2018.. After introducing TOF and PSL, her skin lesions and chest CT findings of ILD gradually improved. Six months after the induction of TOF, the skin ulcer was epithelialized. One year after the introduction of TOF, PSL was decreased to 9 mg, and the disease activity did not re-exacerbate.. This case report is the first report suggesting the effectiveness of TOF for recurrent case of anti-MDA5 Ab-positive cADM with ILD. TOF might be an effective therapeutic option for treating recurrent case of anti-MDA5 Ab-positive cADM.

Topics: Autoantibodies; Dermatomyositis; Female; Humans; Interferon-Induced Helicase, IFIH1; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Recurrence

Topics: Autoantibodies; Dermatomyositis; Humans; Piperidines; Pyrimidines; Pyrroles

Topics: Autoantibodies; Dermatomyositis; Humans; Interferon Type I; Piperidines; Pyrimidines; Pyrroles

Some patients with cutaneous DM demonstrate incomplete responses to conventional therapy while some, including those with extra-cutaneous manifestations, experience disease recurrences. Janus kinase/signal transducers and activators of transcription pathway inhibition has been reported to mitigate IFN signalling, which is thought to contribute to disease pathogenesis in DM. Four cases of refractory DM responsive to tofacitinib have been reported in the literature. Our case series investigated the use of tofacitinib in refractory cutaneous DM.. Our case series includes four subjects with refractory DM who received tofaticinib after failure of several immunosuppressive and immunomodulatory agents.. All four subjects responded well to tofacitinib with significant improvement in cutaneous and extra-cutaneous manifestations.. Tofacitinib can improve cutaneous and inflammatory articular manifestations in refractory DM.

Topics: Adult; Aged; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Janus Kinase Inhibitors; Male; Middle Aged; Piperidines; Pyrimidines; Pyrroles; Retreatment; Treatment Outcome

Dermatomyositis (DM) can be complicated by calcinosis and interstitial lung disease (ILD). Calcinosis can be severely debilitating or life-threatening and to date there is no treatment with proven efficacy. In DM type I interferon contributes to pathophysiology by inducing the expression of proinflammatory cytokines and the JAK-STAT (signal transducer and activator of transcription) pathway may be involved in the regulation of mitochondrial calcium store release, a process potentially important for calcification in DM. JAK-inhibition may therefore be an attractive therapy in DM complicated by calcifications.. We report on the fast and persistent response of extensive and rapidly progressive DM-associated calcifications in two patients treated with the JAK-inhibitor tofacitinib. During the 28-week observation period in both patients no new calcifications formed and existing calcifications were either regressive or stable. Furthermore, concomitant life-threatening DM-associated ILD (acute fibrinous and organizing pneumonia; AFOP) in one patient rapidly responded to tofacitinib monotherapy. Both patients were able to taper concomitant glucocorticoids. Tofacitinib was well tolerated and safe.. The results of our study support the role of JAK/STAT signaling in the development of calcinosis and ILD in DM. Tofacitinib may be an effective and safe treatment for calcinosis in DM and potentially for other connective tissue disease complicated by calcinosis.

Topics: Calcinosis; Dermatomyositis; Female; Humans; Lung Diseases, Interstitial; MAP Kinase Kinase 4; Middle Aged; Piperidines; Pyrimidines; Pyrroles

We aimed to determine the outcome of combination therapy with tofacitinib (TOF) in a case series of refractory rapidly progressive interstitial lung disease (ILD) associated with anti-melanoma differentiation-associated 5 gene (MDA5) antibody-positive (Ab+) DM. Patients who had poor prognostic factors and failed to respond to immunosuppressive therapy were selected for TOF treatment.. Five patients with anti-MDA5 Ab+ DM-ILD who failed to respond to triple therapy with high dose glucocorticoids, CSA and CYC were given additional TOF (10 mg/day). To identify the poor prognostic factors, data from 15 consecutive patients (seven survived and eight died) with anti-MDA5 Ab+ DM-ILD before induction of TOF were analysed.. Three poor prognostic factors were identified: serum ferritin level >1000 ng/ml before therapy; ground-glass opacities in all six lung fields before therapy; and worsening of pulmonary infiltrates during therapy. All six patients who had all of the three factors and received triple therapy died before TOF therapy. There were five patients who had all of the three prognostic factors and failed to respond to triple therapy, but were able to receive the combination therapy with TOF; among them, three survived and two died. The survival rate of patients who received TOF was significantly better than that of the historical controls with immunosuppressive therapy before TOF. The patients who received TOF experienced complicated adverse events, particularly viral infection.. Combination therapy with TOF might have the potential to control refractory anti-MDA5 Ab+ DM-ILD.

Topics: Adult; Aged; Dermatomyositis; Drug Therapy, Combination; Female; Ferritins; Glucocorticoids; Humans; Interferon-Induced Helicase, IFIH1; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Piperidines; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Survival Rate; Treatment Outcome

Topics: Azathioprine; Dermatomyositis; Female; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Methotrexate; Middle Aged; Mycophenolic Acid; Piperidines; Pyrimidines; Pyrroles; Retreatment; Treatment Failure; Treatment Outcome

Topics: Administration, Oral; Adult; Dermatomyositis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple; Female; Follow-Up Studies; Humans; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Sampling Studies; Severity of Illness Index; Treatment Outcome

Topics: Aged, 80 and over; Androstanols; Anesthesia, Intravenous; Anesthetics, Intravenous; Carcinoma, Squamous Cell; Delayed Emergence from Anesthesia; Dermatomyositis; Disease Susceptibility; Female; Humans; Intraoperative Complications; Neuromuscular Nondepolarizing Agents; Parathyroid Neoplasms; Parathyroidectomy; Piperidines; Pneumonia, Aspiration; Preanesthetic Medication; Propofol; Remifentanil; Risk; Rocuronium

Topics: Anesthesia, General; Bundle-Branch Block; Dermatomyositis; Dyslipidemias; Epoprostenol; Female; Fentanyl; Furosemide; Humans; Hypertension; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Mediastinal Diseases; Mediastinoscopy; Methyl Ethers; Middle Aged; Oxygen Inhalation Therapy; Piperidines; Preoperative Care; Raynaud Disease; Remifentanil; Sevoflurane; Spironolactone