The utility of layering systemic therapies in connective tissue diseases

Abstract Background Cutaneous manifestations in connective tissue diseases (CTDs) are often chronic and difficult to control. Objectives This study aims to review the use of combination systemic medications in CTDs and assess disease response. Methods An IRB‐approved, retrospective chart review was conducted at a single large academic institution in New Orleans, Louisiana. Inclusion criteria were adult patients with CTDs on two or more systemic therapies. Results Out of 101 patients, 37.62% were taking combination systemic agents. Of these patients, 44% were diagnosed with lupus, 18% with dermatomyositis (DM), 8% with systemic scleroderma (SSc), 10% with morphea/limited scleroderma (M), 12% with mixed connective tissue disease (MCTD), and 8% with rheumatoid arthritis (RA). The most common regimen for lupus, MCTD, and SSc patients was hydroxychloroquine (HCQ) + prednisone (PRED) + mycophenolate mofetil (MMF). DM patients were most commonly taking combinations of the above regimen with intravenous immunoglobulin (IVIG). Morphea and RA patients were on multiple combinations of steroid and nonsteroidal agents including MMF, IVIG, azathioprine, methotrexate, HCQ, sulfasalazine, upadacitinib, apremilast, and tofacitinib. Conclusions This study aims to assess the efficacy of combination systemic medications and disease response in CTDs. Lupus was the most common CTD in our study, with patients taking 2–4 combination medications. HCQ, MMF, and PRED were the most common medications used within a combination regimen with minimal adverse effects. Though our study has several limitations including its retrospective nature and small sample size, it shows that CTDs can be resistant to monotherapy and that combination therapy might be required. More research in layering systemic agents is needed since this topic is currently limited to minimal case series and clinical trials.