piperidines and Scleroderma--Diffuse

Systemic sclerosis (SSc) is an autoimmune rheumatic disease characterised by vasculopathy, inflammation and fibrosis in multiple organs and occasionally coexists with rheumatic conditions, such as axial spondyloarthritis (axSpA). The aim of this study was to demonstrate the successful use of tofacitinib in SSc and axial spondylarthritis (axSpa), as a novel therapeutic agent; however, further studies are needed to elucidate the role of JAK inhibition in the treatment of both conditions. In this paper, we report a case of a 58-year-old woman with diffuse SSc who developed axSpA. The patient had a 10-year history of SSc and was treated with tocilizumab before the onset of lower back pain. The diagnostic evaluation included MRI that demonstrated bone marrow oedema in the sacroiliac joints, the HLA-B27 was positive, and given the inflammatory features of her back pain, she was diagnosed with axSpa. The biologic agent was switched into etanercept with an improvement of the back pain; however, the patient had a relapse of her skin manifestations. Given the treatment failure, we aim to treat the 2 coexisting conditions concurrently with tofacitinib, which led to symptom improvement. This case report is noteworthy, given the rarity of the coexistence of both conditions and the therapeutic challenges faced by the clinician. The online database MEDLINE/PubMed and Scopus where searched for articles published from inception to June 2020, using the terms "ankylosing spondylitis" AND "systemic sclerosis" OR "axial spondyloarthritis" AND "systemic sclerosis". Also, we searched the American College of Rheumatology and European League Against Rheumatism annual meeting abstracts from 2015 to 2019 using the same terms. As a result, we found 9 similar case reports. 9 case reports of patients with both conditions were identified through a literature review and we highlighted the differences and similarities between them. Also, we emphasise on intracellular signalling inhibitors as novel therapeutic targets in treating both conditions. Tofacitinib might be a novel therapeutic agent in the management of SSc and axSpA.

Topics: Female; Humans; Low Back Pain; Magnetic Resonance Imaging; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Sacroiliac Joint; Scleroderma, Diffuse; Spondylitis, Ankylosing

Topics: Animals; Cannabinoid Receptor Antagonists; Cannabinoids; Fibrosis; Humans; Liver Cirrhosis; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Rimonabant; Scleroderma, Diffuse; Signal Transduction; Skin; Smad Proteins; Transforming Growth Factor beta1

Topics: Humans; Piperidines; Pyrimidines; Scleroderma, Diffuse; Scleroderma, Systemic; Skin

To analyse the effectiveness of tofacitinib for the treatment of refractory skin thickening in dcSSc.. Data from 10 patients with dcSSc treated with tofacitinib (5 mg twice daily) were analysed. A total of 12 dcSSc patients treated with intensive conventional immunosuppressants were selected as the historical comparator group. A clinically relevant response was defined as a decrease in the modified Rodnan skin score (mRSS) of >5 points and ≥25% from baseline. Clinical indicators were compared between the two groups to evaluate the effect of tofacitinib.. The mRSS significantly improved the first month after tofacitinib treatment, with a mean change in the mRSS of -3.7 (95% CI -5.52, -1.88; P = 0.001) and greater than the comparators at 6 months [-10.0 (95% CI -14.74, -5.26) vs -4.1 (95% CI -7.49, -0.73), P = 0.026]. Tofacitinib-treated patients had a significantly shorter response time than the comparators (P = 0.015 by log-rank test), with overall response rates of 20% (2/10) vs 0% (0/12) and 60% (6/10) vs 16.7% (2/12) at 1 and 3 months, respectively.. Our results indicate that tofacitinib may be as effective as or even better than intensive conventional immunosuppressants, with a quicker and higher response rate in refractory dcSSc patients with progressive skin thickness.

Topics: Adult; Aged; Disease Progression; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Scleroderma, Diffuse; Skin; Treatment Outcome; Young Adult