Micofenolato
Há um estudo de fase 2 em andamento estudando os efeitos do micofenolato para melhorar a pele e a função na esclerose sistêmica cutânea limitada.[48]ClinicalTrials.gov. Mycophenolate in limited cutaneous systemic sclerosis (MINIMISE-Pilot) (MINIMISE). NCT04927390. 6 July 2022 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT04927390
treprostinila
Esse análogo da prostaciclina foi submetido a ensaios clínicos para o tratamento do fenômeno de Raynaud e/ou de úlceras digitais.[49]Engel G, Rockson SG. Treprostinil for the treatment of severe digital necrosis in systemic sclerosis. Vasc Med. 2005 Feb;10(1):29-32.
http://www.ncbi.nlm.nih.gov/pubmed/15920997?tool=bestpractice.com
[50]Chung L, Fiorentino D. A pilot trial of treprostinil for the treatment and prevention of digital ulcers in patients with systemic sclerosis. J Am Acad Dermatol. 2006 May;54(5):880-2.
http://www.ncbi.nlm.nih.gov/pubmed/16635673?tool=bestpractice.com
Em um estudo de fase 1 de farmacocinética, aberto, de dois centros, o treprostinil oral foi efetivamente absorvido em 19 pacientes com esclerodermia e foi temporariamente associado à melhora da perfusão cutânea e da temperatura.[51]Shah AA, Schiopu E, Hummers LK, et al. Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther. 2013 Apr 18;15(2):R54.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011881
http://www.ncbi.nlm.nih.gov/pubmed/23597147?tool=bestpractice.com
Anticorpos específicos
Foram realizados estudos direcionados ao fator de transformação de crescimento beta (TGF beta) e a outros sinais pró-fibróticos.[15]Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003.
http://www.ncbi.nlm.nih.gov/pubmed/19420368?tool=bestpractice.com
[52]Abraham DJ, Shiwen X, Black CM, et al. Tumor necrosis factor alpha suppresses the induction of connective tissue growth factor by transforming growth factor-beta in normal and scleroderma fibroblasts. J Biol Chem. 2000 May 19;275(20):15220-5.
http://www.jbc.org/content/275/20/15220.long
http://www.ncbi.nlm.nih.gov/pubmed/10809757?tool=bestpractice.com
Um estudo de fase 1 aberto, multicêntrico, de coorte de escalonamento de dose com AVID200, um novo e potente inibidor do receptor TGF beta, publicou resultados iniciais de que o medicamento foi bem tolerado neste primeiro estudo em pacientes com esclerose sistêmica cutânea difusa (ESCD).[53]ClinicalTrials.gov. Safety and tolerability study of AVID200 in patients with diffuse cutaneous systemic sclerosis. NCT03831438. 23 October 2020 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03831438
[54]Lafyatis R, Spiera R, Domsic R, et al. THU0329 safety, target engagement, and initial efficacy of AVID200, a first-in-class potent and isoform-selective inhibitor of TGF-beta 1 and 3, in patients with diffuse cutaneous systemic sclerosis (DCSSC): a phase 1 dose escalation study. Annals of the Rheumatic Diseases 2020;79:394-5.
https://ard.bmj.com/content/79/Suppl_1/394.2.info
Rituximabe
Estudos preliminares com rituximabe demonstraram melhoras na pele e na função pulmonar.[55]McGonagle D, Tan AL, Madden J, et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford). 2008 Apr;47(4):552-3.
https://academic.oup.com/rheumatology/article/47/4/552/1789092
http://www.ncbi.nlm.nih.gov/pubmed/18281368?tool=bestpractice.com
[56]Daoussis D, Liossis SN, Tsamandas AC, et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010 Feb;49(2):271-80.
http://rheumatology.oxfordjournals.org/content/49/2/271.full
http://www.ncbi.nlm.nih.gov/pubmed/19447770?tool=bestpractice.com
Uma revisão sistemática e metanálise de 2021 concluiu que o rituximabe é uma estratégia promissora para o tratamento da doença pulmonar intersticial associada à esclerose sistêmica e à fibrose cutânea.[57]de Figueiredo Caldas MMV, de Azevedo KPM, de França Nunes AC, et al. Is rituximab effective for systemic sclerosis? A systematic review and meta-analysis. Adv Rheumatol. 2021 Feb 27;61(1):15.
http://www.ncbi.nlm.nih.gov/pubmed/33640020?tool=bestpractice.com
Imatinibe
Foi sugerido que a esclerose sistêmica pode melhorar com o uso de inibidores de tirosina quinase, como imatinibe.[58]Papadakis V, Karakasis D, Sfikakis PP, et al. Is imatinib mesylate a promising drug in scleroderma due to extensive chronic graft-versus-host disease? Leuk Lymphoma. 2009 Mar;50(3):471-4.
http://www.ncbi.nlm.nih.gov/pubmed/19253137?tool=bestpractice.com
[59]Soria A, Cario-André M, Lepreux S, et al. The effect of imatinib (Glivec®) on scleroderma and normal dermal fibroblasts: a preclinical study. Dermatology. 2008;216(2):109-17.
http://www.ncbi.nlm.nih.gov/pubmed/18216472?tool=bestpractice.com
[60]Chung L, Fiorentino DF, Benbarak MJ, et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):584-91.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2638060
http://www.ncbi.nlm.nih.gov/pubmed/19180499?tool=bestpractice.com
Um pequeno estudo revelou que o imatinibe foi pouco tolerado no tratamento da ESCD ativa (principalmente precoce), mas outro estudo de fase 2a, aberto e de braço único, revelou que o imatinibe foi tolerado pela maioria dos 24 pacientes com ESCD.[61]Pope J, McBain D, Petrlich L, et al. Imatinib in active diffuse cutaneous systemic sclerosis: results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum. 2011 Nov;63(11):3547-51.
https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.30549
http://www.ncbi.nlm.nih.gov/pubmed/21769850?tool=bestpractice.com
[62]Spiera RF, Gordon JK, Mersten JN, et al. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011 Jun;70(6):1003-9.
https://ard.bmj.com/content/70/6/1003.long
http://www.ncbi.nlm.nih.gov/pubmed/21398330?tool=bestpractice.com