Chapter 9-06: Key Clinical Trials & Publications in Rheumatology

RHEUMATOID ARTHRITIS

• Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002;359:1173–7.

  • - Prospective observational study that demonstrated a 60% decrease in all-cause mortality and a 70% decrease in cardiovascular mortality among adults with RA treated with methotrexate compared to other DMARDS or prednisone. Decreased all-cause and CV mortality was not seen for sulfasalazine or hydroxychloroquine. This study underscores the notion that systemic inflammation in RA contributes to cardiovascular mortality and that methotrexate ameliorates this.

• The Tight COntrol for Rheumatoid Arthritis (TICORA) Study. Lancet 2004;364:263–269.

  • - Single-blind randomized controlled trial evaluating monthly visits with DMARD titration (MTX, SSZ, HCQ) to a goal disease activity score <2.4 versus q3 mo visits with titration per usual care. Patients in the “intensive management” group had higher rates of remission (65% vs. 16%) at 18 months. This study supported a “treat-to-target” approach using a disease activity score (DAS28 in this case) to guide therapy escalation.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

• A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. New Engl J Med 1991;324:150–154.

  • - Small, double-blind randomized controlled trial that randomized patients to either continue hydroxychloroquine therapy or to replace hydroxychloroquine with placebo for 24 weeks. The relative risk of clinical flare was 2.5x higher in the placebo arm than the hydroxychloroquine. This demonstrated that patients with quiescent SLE on hydroxychloroquine were less likely to have a clinical flare-up if they were maintained on the drug.

• Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009;20:1103–1112.

  • - Randomized, single-blind study comparing IV cyclophosphamide 0.5–1 g/m2 monthly) to PO mycophenolate (3 g/d) for treatment of class III and IV lupus nephritis. Mycophenolate was non-inferior to cyclophosphamide for achieving the primary outcome of decrease in UPCR and stabilization in serum creatinine at 24 weeks. Prior studies established less infections, alopecia, and amenorrhea with mycophenolate compared to cyclophosphamide (New Engl J Med 2005;353:2219 and J Rheum 2011;38:69).

• Development of autoantibodies before the clinical onset of systemic lupus erythematosus. New Engl J Med 2003;349:1526–1533.

  • - Retrospective study of 130 armed forces personnel who provided serum on enlistment and biennially thereafter, showing that autoantibodies including ANA and dsDNA develop years before SLE diagnosis (mean of 3 yr vs. 2.2 yr, respectively). This study suggests that a break in humoral immune tolerance is not sufficient to cause pathology and raises intriguing questions about whether there are additional immunologic and environmental modifying factors (e.g., autoantibody post-translational modifications, infections, microbiome perturbations) needed to cause disease.

SYSTEMIC SCLERODERMA

• Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II Study). Lancet Respir Med 2016;4:708–719.

  • - Randomized controlled, double-blind, parallel group trial that randomized patients with scleroderma-related interstitial lung disease to receive mycophenolate mofetil (target dose: 1500 mg twice daily) for 24 months or oral cyclophosphamide (target dose: 2.0 ...