Adding intravenous methylprednisolone pulses to standard treatment for inducing remission in severe cases of ANCA-associated vasculitis does not confer clinical benefits and increases the risk of infection and diabetes, a study suggests.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis comprises a group of autoimmune diseases where the body attacks it own neutrophils — a type of immune cells. Neutrophil destruction leads to excessive inflammation in small blood vessels of different organs, which can result in organ failure.
Cases of severe ANCA vasculitis can be life threatening if remission is not induced in time. There are different treatments to induce remission, such as plasma exchange — a procedure similar to dialysis performed on the blood plasma — and a pulse of intravenous methylprednisolone, a corticosteroid. These are commonly followed by high doses of oral corticosteroids and cyclophosphamide.
However, corticosteroids should be used carefully as these medications can raise the risk of infections, weight gain, high glucose levels, and diabetes.
Researchers evaluated whether pulses of methylprednisolone were associated with any benefit or harm when used in combination with standard remission therapy in severe ANCA vasculitis patients.
To do so, they recruited 114 newly diagnosed patients from five centers in Europe and the U.S. Participants received standard therapy to induce remission, consisting of plasma exchange, cyclophosphamide, and high-dose oral corticosteroids either with an additional pulse of intravenous methylprednisolone (52 patients, MP group) or without the pulse (62 patients, non-MP group). Researchers evaluated survival, renal recovery, relapses, and adverse events for one year after treatment.
Participants in the two groups were similar in age and type and severity of ANCA-associated vasculitis. The non-MP group had a higher representation of Caucasians.
The overall survival was similar for both groups; 94.2% of patients in the MP and 91.9% in the non-MP groups were alive three months after treatment. The values were 84.6% and 82.3%, respectively, after one year.
The renal recovery and relapse values were also similar. In the MP group, 57.7% of patients achieved renal recovery, and 11.5% of patients had relapses in the year following treatment. The values for the non-MP group were 66.1% and 8.1%, respectively.
Regarding adverse events, the MP group had more and more severe infections, with 44.2% of patients reporting infections, 36.5% of which were severe, In the non-MP group, 24.2% of patients reported infections, 19.4% of which were severe. Most infections happened in the first three months after treatment.
The MP group also had a higher incidence of diabetes, with 26.9% of patients developing it in the year following treatment versus 6.5% in the non-MP group. Most cases were diagnosed in the first month after treatment.
The occurrence of infections and the incidence of diabetes were also related to the dose of intravenous methylprednisolone, with patients receiving higher doses presenting more and more severe adverse events.
The results suggest that “the addition of intravenous pulse MP [methylprednisolone] to standard induction of remission therapy with cyclophosphamide, plasma exchange, and high-dose oral corticosteroids may not confer any benefit in terms of improving patient outcomes and may increase patient harm,” the researchers stated.
“Our data question the widespread use of pulse MP in the treatment of severe [ANCA-associated vasculitis] and indicate the need for an appropriately conducted, randomized, controlled clinical trial to definitively answer the question of whether MP should be used in the treatment of severe AAV and whether there may be a subgroup of patients in whom treatment with MP may be advantageous,” they concluded.