Rituximab offers the same benefits as cyclophosphamide in the treatment of vasculitis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, Pa.
Vasculitis refers to inflammation of blood vessels. There are multiple types of vasculitis. Most types of vasculitis are rare, their causes are generally unknown, and treatment is challenging. ANCA-associated vasculitis is caused by an overreaction of the immune system to many organ systems of the body (a systemic autoimmune disease). There are several types of ANCA-associated vasculitis, including Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome.
Combined use of cyclophosphamide and glucocorticoids has been the standard of care for induction of remission of ANCA-associated vasculitis for decades. Some studies have suggested that rituximab (Rituxan®) may be an effective alternative to cyclophosphamide for treating the disease while avoiding some of the side effects, such as low white blood counts, infections, irritation of the bladder, infertility and others caused by the standard therapy.
Researchers recently set out to compare the effectiveness of rituximab to cyclophosphamide in 197 patients with severe Wegener’s granulomatosis or microscopic polyangiitis.
They divided the participants into two groups; 99 participants on rituximab, of which 85 percent completed the study; and 98 participants on cyclophosphamide, of which 83 percent completed the study. The goal was to get each participant into remission and off prednisone.
Researchers found that 64 percent of the participants on rituximab experienced disease remission, compared to 55 percent of participants on the combination therapy. In addition, 71 percent of patients taking rituximab dropped their BVAS/WG (a composite measure of vasculitis disease activity) to zero and their prednisone (steroid) medication down to under 10 mg/day. This only occurred in 62 percent of the patients in the cyclophosphamide treatment group.
It was also noted that there were no differences between the two groups regarding the rates of disease flares and renal treatment response.
Additionally, the rates of side effects were similar among the two groups, but fewer patients in the rituximab group experienced one or more selected severe side effects.
“This study proves that for patients with severe ANCA-associated vasculitis (Wegener’s granulomatosis and microscopic polyangiitis) there is finally an effective and well tolerated alternative to cyclophosphamide,” explains Ulrich Specks, MD; Mayo Clinic, Rochester, Minn., and lead investigator in the study.
Patients should talk to their rheumatologists to determine their best course of treatment.
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.
Editor’s Notes: Dr. Specks will present this research during the ACR Annual Scientific Meeting at the Pennsylvania Convention Center at 11:30 AM on Wednesday, October 21 in Room 108B. Dr. Specks will be available for media questions and briefing at 1:30 PM on Sunday, October 18 in the on-site press conference room, 109 A.
Presentation Number: 550
Rituximab Versus Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitis: A Randomized Controlled Trial (RAVE)
J.H. Stone, M.D., MPH, Rheumatology Unit, MGH, Boston, MA P.A. Merkel, M.D., MPH, BU, Boston, MA P. Seo, M.D., Division of Rheumatology, Johns Hopkins, Baltimore, MD R. Spiera, M.D., Rheumatology, HSS, New York, NY C.A. Langford, M.D., MHS, Rheumatic and Immunologic Dis, Cleveland Clinic, Cleveland, OH Gary S. Hoffman, M.D., Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH C.G.M. Kallenberg, PhD, Clinical Immu/Rheum T3.242, University Medical Center Groningen, Groningen, Netherlands E. William St. Clair, MD, Dept of Medicine, Duke University Medical Center, Durham, NC B.J. Fessler, MD, UAB, Birmingham, AL N. Tchao, M.D., ITN, San Francisco, CA L. Ding, M.D., NIH, Bethesda, MD L.V. Webber, RN, NIH, Bethesda, MD D. Ikle, PhD, Rho, Chapel Hill, NC D. Weitzenkamp, PhD, Rho, Chapel Hill, NC W. Wu, MS, PPD, Wilmington, NC P. Brunetta, MD , Genentech, Inc., S. San Francisco, CA L. Seismundo, RN, Division of Rheumatology, Johns Hopkins, Baltimore, MD F.C. Fervenza, MD, PhD, Mayo Clinic, Rochester, MN K.A. Keogh, MBBS, Mayo Clinic, Rochester, MN E. Y. Kissin, MD, Rheumatology, BU, Boston, MA K.S. Mieras , Mayo Clinic, Rochester, MN P.A. Monach, MD, PhD, Rheumatology, BU, Boston, MA T. Peikert, M.D., Mayo Clinic, Rochester, MN C. Stegeman, M.D., Clinical Immu/Rheum T3.242, Med.Univ., Groningen, Netherlands S.R. Ytterberg, M.D., Rheumatology Division, Mayo Clinic, Rochester, MN U. Specks, MD, Mayo Clinic, Rochester, MN The RAVE-ITN Research Group , ITN, San Francisco, CA
Purpose: Combined use of cyclophosphamide (CYC) and glucocorticoids (GCS) has been the standard of care for remission induction for ANCA-associated vasculitis (AAV) for decades. Uncontrolled studies suggest rituximab (RTX) may be effective for AAV, and its use may avoid some of the toxicities associated with CYC therapy. This trial compares the efficacy of RTX to that of CYC for AAV.
Method: A multicenter, randomized, double-blind, placebo-controlled trial was conducted to determine if treatment with RTX (375 mg/m2 i.v. weekly x 4) was not inferior to CYC (2 mg/kg/d p.o.) for inducing remission in severe AAV. Once remission was achieved, CYC was replaced by azathioprine between months 3-6. All patients received the same GCS treatment protocol: 1-3 g i.v. methylprednisolone followed by prednisone 1 mg/kg/d p.o. reduced to 40 mg/d by month 1, and then tapered and discontinued completely by month 6. The primary endpoint was disease remission in the absence of prednisone therapy at month 6. Remission was defined as a Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG) of 0.
Results: Nine centers enrolled a total of 197 patients with severe Wegener’s granulomatosis or microscopic polyangiitis (3:1), all positive for PR3-ANCA or MPO-ANCA (2:1). The mean BVAS/WG at enrollment was 8.4 (range 3-19). Disease severity, organ involvement, proportion of newly diagnosed disease (49%), AAV type, and ANCA type were similar in both treatment arms. All results reported refer to the initial 6 months of study participation for each patient. Eighty-four (85%) of the 99 patients in the RTX arm and 81 (83%) of the 98 in the CYC arm completed 6 months of follow-up. Sixty-three (64%) of the patients assigned to RTX achieved the primary outcome, compared with 52 (55%) in the CYC arm (P=0.21). Seventy patients (71%) in the RTX arm achieved a BVAS/WG of 0 and a prednisone dose < 10 mg/day at six months, compared with 61 patients (62%) in the CYC arm (P=0.22). No differences were observed between the groups in the rates of disease flares. The rates of protocol-defined selected adverse events were similar between the RTX and CYC groups (0.06 versus 0.08; P=0.29), but fewer patients in the RTX group experienced one or more of these events (19 vs 32 patients; P=0.03). There was no difference in treatment response within the subgroups with major renal involvement (n=99) or alveolar hemorrhage (n=50).
Conclusion: RTX is not inferior to CYC for the induction of remission in severe AAV. These results provide strong support for the use of RTX as an alternative to CYC in AAV.
Disclosure: J. H. Stone, None; P. A. Merkel, Genentech, Inc., 9 ; P. Seo, None; R. Spiera, None; C. A. Langford, None; G. S. Hoffman, None; C. G. M. Kallenberg, None; E. W. St. Clair, Genentech and Biogen IDEC Inc., 2, Biogen Idec, 5 ; B. J. Fessler, None; N. Tchao, None; L. Ding, None; L. V. Webber, None; D. Ikle, None; D. Weitzenkamp, None; W. Wu, None; P. Brunetta, Genentech,Inc, 3 ; L. Seismundo, None; F. C. Fervenza, Genentech , 2 ; K. A. Keogh, None; E. Y. Kissin, None; K. S. Mieras, None; P. A. Monach, None; T. Peikert, None; C. Stegeman, None; S. R. Ytterberg, None; U. Specks, None; T. RAVE-ITN Research Group, None.
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