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1.
Best Pract Res Clin Rheumatol ; : 101945, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38627168

ABSTRACT

Fibrosis is commonly associated with chronic rheumatic diseases, and causes substantial morbidity and mortality. Treatment of fibrosis is extremely challenging but is badly needed, as approved antifibrotic therapies fibrosis do not halt its progression, which will be discussed with a focus on pulmonary fibrosis. Findings from recent studies indicate several therapeutic targets for treating fibrosis. Interleukin-11 is emerging as a fibrogenic cytokine whose activity can be blocked with neutralizing monoclonal antibodies. Fibroblast activation protein (FAP) is highly expressed by activated fibroblasts in inflammatory and fibrotic tissues. Targeting FAP with different modalities has been extensively explored as adjunct treatment for cancer, which can also apply to treating fibrosis in rheumatic diseases.

2.
Immunotherapy ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530074

ABSTRACT

Axial spondyloarthritis is a chronic, immune-mediated systemic inflammatory disease encompassing ankylosing spondylitis and nonradiographic axial spondyloarthritis. TNF inhibitors are the preferred second line therapy for patients with active axial spondyloarthritis. Certolizumab pegol is a TNF inhibitor approved for treatment of both. Three large phase III trials (RAPID-axSpA, C-axSpAnd and C-OPTIMISE) and one large phase IV trial (CIMAX) establish its clinical efficacy in treatment of active disease and maintenance of remission for both diseases. Real world evidence demonstrates clinical efficacy and benefits including reduced bone loss, reduced risk of uveitis, safety in pregnancy and lactation and index drug survival of 10 years. It is generally well tolerated, though can be associated with increased risk of serious infections.


Axial spondyloarthritis is a chronic (long-lasting) autoimmune disease encompassing two other inflammatory conditions called ankylosing spondylitis and nonradiographic axial spondyloarthritis. A type of medicines, called tumor necrosis factor inhibitors, are the preferred second-line medicines for patients with active axial spondyloarthritis. Second line is treatment for a condition after the initial treatment has failed. Certolizumab pegol is one of these medicines approved for the treatment of both. Four large phase III or IV studies (RAPID-axSpA, C-axSpAnd, C-OPTIMISE and CIMAX) establish its effectiveness in the treatment of active disease and maintenance of remission (a period where disease symptoms have become less severe) for both diseases. Studies of its use in routine healthcare delivery show clinical efficacy (or effectiveness) and benefits including reduced bone loss, reduced risk of certain eye disease (uveitis), safety in pregnancy and lactation and 10-year effectiveness before the need for a medication change. It is generally well tolerated, though can be associated with increased risk of serious infections.

6.
Arthritis Rheumatol ; 73(12): 2151-2160, 2021 12.
Article in English | MEDLINE | ID: mdl-34697918

ABSTRACT

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.


Subject(s)
Antimalarials/therapeutic use , COVID-19 Drug Treatment , Cardiotoxicity/etiology , Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , Antimalarials/adverse effects , Chloroquine/adverse effects , Humans , Hydroxychloroquine/adverse effects
7.
Lung ; 199(2): 147-153, 2021 04.
Article in English | MEDLINE | ID: mdl-33825964

ABSTRACT

This is a prospective, open-label, proof-of-concept study of tofacitinib, a Janus kinase inhibitor, as a steroid-sparing therapy in corticosteroid-dependent pulmonary sarcoidosis. Five patients with corticosteroid-dependent pulmonary sarcoidosis were treated with tofacitinib 5 mg twice daily. The primary endpoint was a ≥ 50% reduction in corticosteroids at week 16 with no worsening in pulmonary function or respiratory symptoms. 60% of patients (3/5) met the primary endpoint. One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis. The three patients who met the primary endpoint each tapered to ≤ 5 mg/day prednisone, respiratory symptoms improved, and spirometry remained stable. In this proof-of-concept study, the addition of a JAK-inhibitor allowed 60% of patients with pulmonary sarcoidosis to successfully taper corticosteroids. JAK-inhibitors are a promising therapy for pulmonary sarcoidosis, which require further investigation in randomized trials.Trial Registration clinicaltrials.gov NCT03793439; registered Jan 4, 2019.


Subject(s)
Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Sarcoidosis, Pulmonary/drug therapy , Adult , Female , Glucocorticoids/administration & dosage , Humans , Male , Middle Aged , Pilot Projects , Prednisone/administration & dosage , Proof of Concept Study , Prospective Studies , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/physiopathology , Spirometry , Treatment Outcome
9.
Arthritis Rheumatol ; 73(6): 908-911, 2021 06.
Article in English | MEDLINE | ID: mdl-33559327

ABSTRACT

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is <2% for usage up to 10 years. Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient's visual function. Baseline testing is advised to rule out confounding disease when a patient is started on HCQ. Annual screening with sensitive tests should begin no more than 5 years after treatment initiation. Providers should be sensitive to the medical value of HCQ, and not stop the drug for uncertain indications. It is important to note that effective communication among prescribing physicians, patients, and eye care providers will optimize the utility and safety of HCQ.


Subject(s)
Antirheumatic Agents/adverse effects , Hydroxychloroquine/adverse effects , Retinal Diseases/chemically induced , Deprescriptions , Dermatology , Humans , Mass Screening , Ophthalmology , Retinal Diseases/diagnosis , Retinal Diseases/ethnology , Rheumatology , Societies, Medical , Tomography, Optical Coherence , Visual Field Tests
12.
J Rheumatol ; 46(7): 748-750, 2019 07.
Article in English | MEDLINE | ID: mdl-30442822

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of anakinra in inpatient management of acute gout and pseudogout. METHODS: Hospitalized patients with acute gout (n = 77) or pseudogout (n = 11) or both (n = 3) were analyzed for response to anakinra and adverse effects. RESULTS: Half of all patients had comorbidities limiting the treatment choice. Anakinra was well tolerated, and 92% of gout flares and 79% of pseudogout flares responded to treatment. CONCLUSION: Anakinra is an effective and safe treatment for acute gout and pseudogout in hospitalized patients, particularly in those with comorbidities.


Subject(s)
Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Arthritis, Gouty/drug therapy , Chondrocalcinosis/drug therapy , Hospitals, University , Interleukin 1 Receptor Antagonist Protein/adverse effects , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Acute Disease , Aged , Antirheumatic Agents/administration & dosage , Comorbidity , Female , Hospitalization , Humans , Injections, Subcutaneous , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Male , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Expert Opin Biol Ther ; 16(8): 1059-64, 2016 08.
Article in English | MEDLINE | ID: mdl-27366922

ABSTRACT

INTRODUCTION: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the spine and sacroiliac (SI) joints. The spectrum of axSpA includes ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Evidence has supported the use of TNF alpha inhibitors (TNFi) in treating these diseases, with good efficacy and tolerable safety profiles. Certolizumab pegol (CZP) is an anti-TNF alpha (TNFa) agent with data to support its use in both AS and nr-axSpA. AREAS COVERED: The pharmacologic properties of CZP were reviewed. Data regarding the use and efficacy of CZP in axSpA were reviewed. Quality of life outcomes and safety profiles of CZP in axSpA patients were discussed as well. EXPERT OPINION: While there are several biologics with evidence for improved outcomes in AS, there is less evidence for biologic medications that have good efficacy in nr-axSpA. CZP has good evidence of improved outcomes in terms of clinical efficacy, patient reported outcomes and imaging outcomes in both conditions, with a tolerable safety profile.


Subject(s)
Certolizumab Pegol/therapeutic use , Spondylarthritis/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Humans , Quality of Life , Spondylitis, Ankylosing/drug therapy
14.
Chest ; 149(4): e99-e101, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27055719

ABSTRACT

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon disease that is the most serious complication associated with unresolved pulmonary embolism. This disease has several risk factors, but no familial pattern has been described. Few thrombophilic conditions have been reported to increase risk of CTEPH, and none of the hereditary thrombophilias causes this disease. The reason CTEPH develops in some patients after pulmonary embolism remains unknown. We describe a 54-year-old woman and her maternal aunt who both underwent pulmonary thromboendarterectomy for CTEPH. This represents the first description of familial CTEPH.


Subject(s)
Hypertension, Pulmonary/etiology , Pedigree , Pulmonary Embolism/complications , Thrombophilia/complications , Chronic Disease , Endarterectomy , Family , Female , Humans , Hypertension, Pulmonary/genetics , Middle Aged , Pulmonary Embolism/genetics , Pulmonary Embolism/surgery , Thrombophilia/genetics
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