Download PDF
Semin Respir Crit Care Med 2017; 38(04): 532-537
DOI: 10.1055/s-0037-1603768
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sarcoidosis: Drugs under Investigation

Jonas Christian Schupp
1   Department of Pneumology, Medical Center - University of Freiburg, Medical Faculty, University of Freiburg, Germany
2   Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, New Haven, Connecticut
,
Björn Christian Frye
1   Department of Pneumology, Medical Center - University of Freiburg, Medical Faculty, University of Freiburg, Germany
,
Gernot Zissel
1   Department of Pneumology, Medical Center - University of Freiburg, Medical Faculty, University of Freiburg, Germany
,
Joachim Müller-Quernheim
1   Department of Pneumology, Medical Center - University of Freiburg, Medical Faculty, University of Freiburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
27 July 2017 (online)

    Permissions and Reprints

Abstract

Etiology of sarcoidosis is still elusive, yet there has been considerable progress in various areas of basic and clinical research. In this review, we focus on ongoing or recently completed clinical–pharmacological studies in patients with sarcoidosis. Positive studies were published in well-characterized and homogenous subcohorts of sarcoid patients. Several drugs have shown a positive effect on sarcoidosis-associated fatigue, cutaneous sarcoidosis, and pulmonary hypertension in sarcoid patients. It seems that the recruitment of clinically precisely defined subcohorts is necessary to achieve positive outcomes in studies on sarcoidosis.

Keywords

sarcoidosis - drugs - clinical trials - review - treatment - human
 

  • References

  • 1 Drent M, Lower EE, De Vries J. Sarcoidosis-associated fatigue. Eur Respir J 2012; 40 (01) 255-263
    CrossrefPubMedGoogle Scholar
  • 2 Lower EE, Malhotra A, Surdulescu V, Baughman RP. Armodafinil for sarcoidosis-associated fatigue: a double-blind, placebo-controlled, crossover trial. J Pain Symptom Manage 2013; 45 (02) 159-169
    CrossrefPubMedGoogle Scholar
  • 3 Lower EE, Harman S, Baughman RP. Double-blind, randomized trial of dexmethylphenidate hydrochloride for the treatment of sarcoidosis-associated fatigue. Chest 2008; 133 (05) 1189-1195
    CrossrefPubMedGoogle Scholar
  • 4 Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet 2014; 383 (9923): 1155-1167
    CrossrefPubMedGoogle Scholar
  • 5 Baughman RP, Strohofer SA, Buchsbaum J, Lower EE. Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis. J Lab Clin Med 1990; 115 (01) 36-42
    PubMedGoogle Scholar
  • 6 Baughman RP, Judson MA, Ingledue R, Craft NL, Lower EE. Efficacy and safety of apremilast in chronic cutaneous sarcoidosis. Arch Dermatol 2012; 148 (02) 262-264
    CrossrefPubMedGoogle Scholar
  • 7 Pariser RJ, Paul J, Hirano S, Torosky C, Smith M. A double-blind, randomized, placebo-controlled trial of adalimumab in the treatment of cutaneous sarcoidosis. J Am Acad Dermatol 2013; 68 (05) 765-773
    CrossrefPubMedGoogle Scholar
  • 8 Brines M, Dunne AN, van Velzen M. , et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Mol Med 2015; 20 (01) 658-666
    PubMedGoogle Scholar
  • 9 Heij L, Niesters M, Swartjes M. , et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 2012; 18: 1430-1436
    CrossrefPubMedGoogle Scholar
  • 10 Dahan A, Dunne A, Swartjes M. , et al. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Mol Med 2013; 19: 334-345
    CrossrefPubMedGoogle Scholar
  • 11 Baughman RP, Culver DA, Cordova FC. , et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest 2014; 145 (04) 810-817
    CrossrefPubMedGoogle Scholar
  • 12 Judson MA, Highland KB, Kwon S. , et al. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis 2011; 28 (02) 139-145
    PubMedGoogle Scholar
  • 13 Judson MA, Baughman RP, Costabel U. , et al. Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis. Eur Respir J 2014; 44 (05) 1296-1307
    CrossrefPubMedGoogle Scholar
  • 14 Diaz-Guzman E, Farver C, Parambil J, Culver DA. Pulmonary hypertension caused by sarcoidosis. Clin Chest Med 2008; 29 (03) 549-563 , x
    CrossrefPubMedGoogle Scholar
  • 15 Ford HJ, Baughman RP, Aris R, Tilley SL, Engel P, Donohue JF. Tadalafil for sarcoidosis associated pulmonary hypertension. Am J Respir Crit Care Med 2014; 189: A4798
    PubMedGoogle Scholar
  • 16 Droitcourt C, Rybojad M, Porcher R. , et al. A randomized, investigator-masked, double-blind, placebo-controlled trial on thalidomide in severe cutaneous sarcoidosis. Chest 2014; 146 (04) 1046
    CrossrefPubMedGoogle Scholar
  • 17 Müller-Quernheim J, Saltini C, Sondermeyer P, Crystal RG. Compartmentalized activation of the interleukin 2 gene by lung T lymphocytes in active pulmonary sarcoidosis. J Immunol 1986; 137 (11) 3475-3483
    PubMedGoogle Scholar
  • 18 Hunninghake GW, Crystal RG. Mechanisms of hypergammaglobulinemia in pulmonary sarcoidosis. Site of increased antibody production and role of T lymphocytes. J Clin Invest 1981; 67 (01) 86-92
    CrossrefPubMedGoogle Scholar
  • 19 Sweiss NJ, Lower EE, Mirsaeidi M. , et al. Rituximab in the treatment of refractory pulmonary sarcoidosis. Eur Respir J 2014; 43 (05) 1525-1528
    CrossrefPubMedGoogle Scholar
  • 20 Jawad S, Liu B, Agron E, Nussenblatt RB, Sen HN. Elevated serum levels of interleukin-17A in uveitis patients. Ocul Immunol Inflamm 2013; 21 (06) 434-439
    CrossrefPubMedGoogle Scholar
  • 21 Dick AD, Tugal-Tutkun I, Foster S. , et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 2013; 120 (04) 777-787
    CrossrefPubMedGoogle Scholar
  • 22 Letko E, Yeh S, Foster CS, Pleyer U, Brigell M, Grosskreutz CL. ; AIN457A2208 Study Group. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology 2015; 122 (05) 939-948
    CrossrefPubMedGoogle Scholar
  • 23 Maya JR, Sadiq MA, Zapata LJ. , et al. Emerging therapies for noninfectious uveitis: what may be coming to the clinics. J Ophthalmol 2014; 2014: 310329
    PubMedGoogle Scholar
  • 24 Dalm VA, van Hagen PM, Krenning EP. The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis. Q J Nucl Med 2003; 47 (04) 270-278
    PubMedGoogle Scholar
  • 25 Gettig J, Cummings JP, Matuszewski K. H.p. Acthar gel and cosyntropin review: clinical and financial implications. P T 2009; 34 (05) 250-257
    PubMedGoogle Scholar
  • 26 Drake WP, Dhason MS, Nadaf M. , et al. Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis. Infect Immun 2007; 75 (01) 527-530
    CrossrefPubMedGoogle Scholar
  • 27 Allen SS, Evans W, Carlisle J. , et al. Superoxide dismutase A antigens derived from molecular analysis of sarcoidosis granulomas elicit systemic Th-1 immune responses. Respir Res 2008; 9: 36
    CrossrefPubMedGoogle Scholar
  • 28 Drake WP, Richmond BW, Oswald-Richter K. , et al. Effects of broad-spectrum antimycobacterial therapy on chronic pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2013; 30 (03) 201-211
    PubMedGoogle Scholar
  • 29 Palinski W. Immunomodulation: a new role for statins?. Nat Med 2000; 6 (12) 1311-1312
    CrossrefPubMedGoogle Scholar
  • 30 Siepmann K, Huber M, Stübiger N, Deuter C, Zierhut M. Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients. Graefes Arch Clin Exp Ophthalmol 2006; 244 (07) 788-794
    CrossrefPubMedGoogle Scholar
  • 31 Buenestado A, Grassin-Delyle S, Guitard F. , et al. Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide. Br J Pharmacol 2012; 165 (06) 1877-1890
    CrossrefPubMedGoogle Scholar
  • 32 Julian MW, Shao G, Schlesinger LS. , et al. Nicotine treatment improves Toll-like receptor 2 and Toll-like receptor 9 responsiveness in active pulmonary sarcoidosis. Chest 2013; 143 (02) 461-470
    CrossrefPubMedGoogle Scholar
  • 33 Hunninghake GW. Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis 1984; 129 (04) 569-572
    PubMedGoogle Scholar
  • 34 Ruperto N, Brunner HI, Quartier P. , et al; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012; 367 (25) 2396-2406
    CrossrefPubMedGoogle Scholar
  • 35 Alten R, Gomez-Reino J, Durez P. , et al. Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet Disord 2011; 12: 153
    CrossrefPubMedGoogle Scholar
  • 36 Ford HJ, Baughman RP, Aris R, Engel P, Donohue JF. Tadalafil therapy for sarcoidosis-associated pulmonary hypertension. Pulm Circ 2016; 6 (04) 557-562
    CrossrefPubMedGoogle Scholar
  • 37 Baughman RP, Drent M, Culver DA. , et al. Endpoints for clinical trials of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2012; 29 (02) 90-98
    PubMedGoogle Scholar
  • 38 Moller DR. Negative clinical trials in sarcoidosis: failed therapies or flawed study design?. Eur Respir J 2014; 44 (05) 1123-1126
    CrossrefPubMedGoogle Scholar