Background/Purpose:
The great majority of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) achieve disease remission initially, but relapses occur in up to 50% of patients within three years. Most disease flares are limited rather than severe. The most common approach to treating limited flares is to increase the glucocorticoid dose with or without a change in other immunomodulatory therapy. However, the effectiveness of this approach has never been studied.
Methods:
This analysis explored the outcomes of patients with a first limited flare in the RAVE trial. Limited flares (BVAS/WG ≤ 3 and no major BVAS/WG items) were treated, per protocol, by increasing prednisone to a dose selected by the investigator. The new prednisone dose was maintained for 1 month before resumption of a protocol-specified taper with an endpoint of 0mg. Patients were followed for 18 months from study entry. The primary outcome was the percentage of patients who achieved and maintained remission without additional changes in therapy.
Results:
47 patients (24%) experienced limited flares and were treated with an increase in prednisone. 25 limited flares occurred in the rituximab (RTX) group and 22 in the cyclophosphamide/azathioprine (CYC/AZA) group. 38 patients (81%) who flared were PR3-ANCA-positive and 29 (62%) had relapsing disease at baseline. 41 patients (87%) achieved remission before experiencing their first limited flare, which occurred on average 7.6 months (range 1.8-17.2) after entry. 28 patients (60%) who experienced a limited flare were off prednisone at the time of the flare, and the mean daily dose at flare among patients who remained on prednisone was 7.1 mg (range 2.5-20.0). Within the CYC/AZA group, 9% of the patients with limited flares were still receiving CYC and 86% were on azathioprine.
Following the limited flare, patients were followed for an average of 7.0 months (range 0.7-16.3). The average daily prednisone dose used to treat limited flares was 19.5mg (range 2.5-80). 36 patients (77%), (18 RTX and 18 CYC/AZA) achieved remission again, an average of 2.5 months after the increase in prednisone dose. However, 26 patients (55%) were unable to achieve and maintain remission throughout the follow-up period: 15 failed to sustain remission and 11 did not reach remission. 22 patients (47%) had recurrent flares: 13 limited (8 RTX, 5 CYC/AZA) and 9 severe (5 RTX, 4 CYC/AZA). Of these, 9 had discontinued prednisone and 13 patients were receiving 7.7mg (range 2.5-20) of prednisone on average. One patient had persistently elevated BVAS/WG (i.e., did not achieve remission again), and three withdrew from the trial. Only 11 patients (23%) who experienced limited flares were able to achieve remission, discontinue prednisone, and maintain remission through month 18.
Conclusion:
Treatment of limited flares in AAV with a temporary increase of glucocorticoids is effective in restoring disease control in most patients, but recurrent flares within a relatively short time period are the rule in this scenario. Alternative approaches to the treatment of limited flares, including continuing glucocorticoids indefinitely or increasing or changing concomitant immunosuppressive therapies, must be considered.
Disclosure:
E. Miloslavsky,
Genentech and Biogen IDEC Inc.,
9;
U. Specks,
None;
P. A. Merkel,
None;
P. Seo,
None;
R. F. Spiera,
Roche Pharmaceuticals, g,
2;
C. A. Langford,
Bristol-Myers Squibb,
9,
Genentech and Biogen IDEC Inc.,
9;
G. S. Hoffman,
None;
C. G. M. Kallenberg,
Roche,
8;
E. W. St. Clair,
Biogen Idec,
9,
Up-to-Date,
7;
N. Tchao,
None;
L. Ding,
None;
D. Ikle,
Rho,
3;
B. Jepson,
Rho,
3;
P. Brunetta,
Genentech Inc,
3;
J. H. Stone,
Genentech and Biogen IDEC Inc.,
2,
Genentech and Biogen IDEC Inc.,
5,
Roche Pharmaceuticals,
2.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-glucocorticoids-to-treat-limited-flares-in-anca-associated-vasculitis/