Two new drugs for rheumatoid arthritis

doi:10.1136/dtb.2017.8.0526

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Approved by FDA in 2018, baricitinib is the second JAK inhibitor for RA treatment that selectively and reversibly inhibits JAK1 and JAK2 and then modulates JAK-STATs intracellular signaling pathways ( 369 , 370 ). Baricitinib also inhibits the effects of JAK3, TyK2, tyrosine-protein kinase Met (c-MET) and Checkpoint kinase 2 (Chk2) ( 371 ).…”

Section: Tsdmards Targeting Jaksmentioning

confidence: 99%

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

et al. 2021

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Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a “trial-and-error” approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.

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Section: Tsdmards Targeting Jaksmentioning

confidence: 99%

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

et al. 2021

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“…Leflunomide is a disease-modifying drug harboring anti-inflammatory and immunomodulatory properties, and is FDA approved for treatment of rheumatoid arthritis and psoriatic autoimmune arthritis in people due to the ability to limit damage to joints by helping to maintain integrity of articular cartilage and bone. 6 The primary metabolite of leflunomide (A77-1726) inhibits pyrimidine synthesis through reversible selective inhibition of dihydroorotate dehydrogenase and subsequent inhibition of activated B and T lymphocytes resulting in dampened proinflammatory signaling and reduced neutrophil infiltration. 1,[7][8][9][10][11][12][13][14] Leflunomide's efficacy for management of rheumatoid arthritis is comparable to methotrexate with respect to improved clinical signs and slowing progression of joint damage.…”

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confidence: 99%

Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs

Chesne,

Doornink,

Sri-Jayantha

et al. 2024

javma

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OBJECTIVE To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA). ANIMALS 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months’ follow-up after starting leflunomide. METHODS Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. RESULTS Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. CLINICAL RELEVANCE Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

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Baricitinib: A Review in Rheumatoid Arthritis

Al-Salama

Scott

2018

Drugs

116

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Baricitinib (Olumiant) is an oral, targeted synthetic DMARD that inhibits JAK1 and JAK2, which are implicated in the pathogenesis of rheumatoid arthritis (RA). This novel, small molecule is approved for use as monotherapy, or in combination with methotrexate, for the treatment of adults with moderate to severe active RA who responded inadequately to or were intolerant of ≥ 1 DMARD. In pivotal multinational trials, once-daily baricitinib 4 mg, with/without methotrexate (± another csDMARD), improved the signs and symptoms of RA, disease activity and physical function in DMARD-naive patients and in patients with an inadequate response to methotrexate, csDMARDs or TNF inhibitors; baricitinib treatment also slowed structural joint damage in DMARD-naive patients and in those with an inadequate response to methotrexate and csDMARDs. Baricitinib plus methotrexate was more effective than adalimumab plus methotrexate in patients with an inadequate response to methotrexate. The onset of these benefits was generally rapid and sustained over time. Baricitinib was generally well tolerated during up to 5.5 years' treatment; the most commonly reported adverse drug reactions were upper respiratory tract infections, increased LDL cholesterol, nausea and thrombocytosis. Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of ≥ 1 DMARD, and extends the options available for this population.

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Two new drugs for rheumatoid arthritis

Cited by 3 publications

References 13 publications

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

Toward Overcoming Treatment Failure in Rheumatoid Arthritis

Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs

Baricitinib: A Review in Rheumatoid Arthritis

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