Team: ALMS Trial
Region: Jump Ball
Authors: University of Alabama at Birmingham Rheumatology Fellowship Program. Maria Salgado Guerrero, MD, second year fellow, Vijay Kannuthurai, MD, second year fellow, Mariana Urquiaga Changanaqui, MD, second year fellow, Joanna Potera, MD, first year fellow, T. Alex Edgil, MD, first year fellow, Haneen Abdalhadi, MD, first year fellow, John Bridges, MD, fourth year combined adult/pediatric rheumatology fellow, Amanda S. Alexander, MD, Assistant Professor, University of Alabama at Birmingham.
Team Overview
2009 is remembered for all-time NBA great Kobe Bryant securing his 4th NBA Championship trophy; however, 2009 can also be remembered for one of the all-time great trials in Rheumatology history — the ALMS trial. Lupus nephritis affects more than half of patients with lupus and increases morbidity and mortality, especially in non-white patients 2. Prior to the Aspreva Lupus Management Study (aka
the ALMS trial), high-dose cyclophosphamide using the “NIH protocol” was standard of care treatment for proliferative lupus nephritis 3. While dose-reduction was proven effective with the EuroLupus regimen, the high toxicity issues of cyclophosphamide remained 4. The ALMS trial was one of the largest lupus trials at its time of publication with 370 patients from 88 centers in 20 countries; and was particularly diverse with a group of patients from all over the world 1. In this multinational cohort, no significantly detectable difference in response rate between MMF and cyclophosphamide was found. There were no significant differences in the rate of adverse events between the two treatment groups. An important subgroup analysis revealed that efficacy of cyclophosphamide in patients of Hispanic or African descent was reduced compared to other race/ethnicity subgroups, and that mycophenolate was consistently effective in all racial and ethnic groups.
Impact on Rheumatology
In a disease that disproportionately affects reproductive age women of color, the impact of a large and racially diverse study with implications related to lowering malignancy and infertility risks cannot be understated. Gonadal toxicity, infectious risk, bladder malignancy, and hematologic toxicity all pose serious possible complications to the use of cyclophosphamide in treating proliferative lupus nephritis. In addition, the inconvenience and higher resource burden of intravenous therapy are other factors that limit its use and accessibility for patients. This was one of the largest and most racially diverse studies for the treatment of lupus nephritis at its time. Dirk Nowitzki, Yao Ming, Giannis Antetokounmpo, the ALMS trial — all great examples how diversity improves the field as a whole. Because of these findings, these treatment principles can be extrapolated to diverse populations across the world affected by lupus nephritis. In place of hospital admission or infusion center access, this practice-changing study (we’re talking about practice!) showed equivalent benefit of therapy with oral medications without dedicated facilities and supervision by healthcare providers.
Chances in the Tournament
The ALMS trial is certainly a fan favorite—the saving grace for the struggling rheumatology fellow that hopes to avoid another sleepless night looking up cyclophosphamide dosing regimen and MESNA calculations. Why use cyclophosphamide after reading the ALMS trial? Hydroxychloroquine withdrawal won’t save rheum fellows any sleepless nights, so you might as well consider the first round a bye and go ahead and face the ALMS trial off against RAVE (another trial notably forcing patients to sit through infusions). No matter who wins the ALMS-RAVE match-up, cyclophosphamide is the loser.
Next scouting report: LUMINA
Back to the full list of scouting reports.
See the Q&A on theMednet.org for the Jump Ball region:
- Do you ever consider discontinuing hydroxychloroquine SLE patients in longstanding remission except in cases of overt toxicity?
- Is there a role for monitoring serum ANCAs to assess ANCA associated vasculitis disease activity?
References:
- Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. Journal of the American Society of Nephrology : JASN. 2009 May 2009;20(5)doi:10.1681/ASN.2008101028
- Dooley MA, Hogan S, Jennette C, Falk R. Cyclophosphamide therapy for lupus nephritis: poor renal survival in black Americans. Glomerular Disease Collaborative Network. Kidney international. 1997 Apr 1997;51(4)doi:10.1038/ki.1997.162
- McCune WJ, Golbus J, Zeldes W, Bohlke P, Dunne R, Fox DA. Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. The New England journal of medicine. 06/02/1988 1988;318(22)doi:10.1056/NEJM198806023182203 4. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis and rheumatism. 2002 Aug 2002;46(8)doi:10.1002/art.10461
