TY - JOUR T1 - Pharmacodynamic monitoring of (immuno)proteasome inhibition during bortezomib treatment of a critically ill patient with lupus nephritis and myocarditis JF - Lupus Science & Medicine DO - 10.1136/lupus-2015-000121 VL - 2 IS - 1 SP - e000121 AU - Karina A de Groot AU - Michel Tsang a Sjoe AU - Denise Niewerth AU - Jacqueline Cloos AU - Jonathan L Blank AU - Hans W M Niessen AU - Sonja Zweegman AU - Alexandre E Voskuyl AU - Gerrit Jansen AU - Joost W van der Heijden Y1 - 2015/12/01 UR - http://lupus.bmj.com/content/2/1/e000121.abstract N2 - Objective To describe the pharmacodynamic monitoring of (immuno)proteasome inhibition following treatment with bortezomib in a therapy-refractory systemic lupus erythematosus (SLE) patient with life-threatening myocarditis and lupus nephritis.Patient and methods Inhibition of catalytic activities of the proteasome subunits β5 (constitutive proteasome), β5i and β1i (immunoproteasome) were measured in peripheral blood mononuclear cells using subunit-specific fluorogenic peptide substrates in a patient who received three cycles of bortezomib (1.3 mg/m2 subcutaneously, days 1, 4, 8 and 11; every three weeks) along with plasma exchange during the first two cycles.Results Proteasome β5, β5i and β1i subunit activities were readily inhibited 1 h after bortezomib administration. Twenty-four hours post-bortezomib administration, β5 and β5i activities were largely restored, whereas inhibition of β1i activity was sustained. Clinically, after three cycles, cardiac function had improved, with concurrent improvement of haemodynamic stability during haemodialysis. Anti-ds-DNA dropped from >400 to 12 IU/mL along with normalisation of complement C3 and C4. Bortezomib therapy was well tolerated, and patient now has a sustained remission for >16 months.Conclusions This case illustrates the potential benefit of pharmacodynamic monitoring of (immune)proteasome subunit-specific activity after bortezomib dosing in patients with therapy refractory SLE. This tool may hold potential to guide personalised/precision dosing aiming to achieve maximal efficacy and minimal toxicity. ER -