Ask the Expert
If you look in current texts, or even on this web site, you do not easily find answers to these very basic questions. The reasons clear answers are hard to come by reflect the great diversity of clinical manifestations of lupus, its proclivity to flare and remit unpredictably, and the long follow-up times necessary to demonstrate superiority of treatment protocols.
The only credible studies that have addressed the issue of duration of treatment are the long-term studies initiated at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health (NIH) decades ago. In these studies, which have been periodically updated, intravenous cyclophosphamide given with prednisone monthly for 6 months followed by 2 additional years of infusions given every 3 months, or azathioprine continued for 2 years, resulted in fewer renal flares and better long-term (10 year) renal outcome than did monthly intravenous cyclophosphamide and daily oral cyclophosphamide or azathioprine for 6 months[1],[2],[3]. vasculitis and in lupus, several recent studies from England and from continental Europe now suggest that a short, 3 month, induction course of cyclophosphamide followed by azathioprine or mycophenolate mofetil (for unspecified times) result in durable remissions. These studies do not address the length of oral treatment nor very long-term outcomes; indeed, most look at outcomes at no more than 1 or 2 years. Although the vasculitis studies may have implications for non-renal SLE, no duration of immunosuppressive therapy studies exist for other non-renal manifestations of disease, for instance brain or spinal cord lupus, thrombocytopenia, or hemolytic anemia. Protocol studies with experimental agents usually treat for induction only, then await recurrence before retreating.
That said, a reasonable rule for the clinician to follow might be: in the treatment of renal lupus, immunosuppression can be withdrawn after 2 years in those patients who are clinically (and serologically?) inactive. For treatment of non-renal lupus, one can consider withdrawal of azathioprine or mycophenolate mofetil after a full year of clinical quiescence. In patients who remain clinically active with either renal or non-renal lupus, it is common practice to continue azathioprine or mycophenolate mofetil indefinitely. The cumulative toxicity of cyclophosphamide (especially marrow fibrosis, hemorrhagic cystitis, and bladder cancer) prohibits its continued use after 2 years. In the event of recurrent flare, re-treatment with any of the immunosuppressive medications is possible; multiple recurrent flares require ad hoc treatment decisions highly tailored to the specific circumstances of the patient. See the complete article on the Hospital for Special Surgery’s web site
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[1] Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Pando J, Steinberg AD, Gourley MF, Klippel JH, Balow JE, Boumpas DT. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002 Apr;46(4):995-1002. [2] Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001 Aug 21;135(4):248-57. [3] Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996 Oct 1;125(7):549-57.
