Rituxan May Be Effective in Treating Refractory AAV Patients, Study Says

Rituxan (rituximab) treatment is effective in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) who failed to respond to standard immunosuppressors, results from a Turkish study suggest.

But the team at Istanbul University noted that key data on its use — especially long-term data — is still lacking.

The research, “Rituximab for anti-neutrophil cytoplasmic antibodies-associated vasculitis: experience of a single center and systematic review of non-randomized studies,” appeared in the journal Rheumatology International.

Cyclophosphamide, an  immunosuppressant, and glucocorticoids have been the standard treatment for remission in AAV. This combination, along with other medications such as anti-hypertensive and renal replacement therapies, are seen to greatly improve outcomes at one year. But troubling side effects can accompany therapies that suppress the immune system, and not all patients respond well to these standard treatments.

Research has shown that Rituxan is comparable to cyclophosphamide in inducing AAV remission, and can be superior in patients who have had a severe disease relapse. However, these studies have some significant limitations, including a large percentage of newly diagnosed patients, and they excluded people with refractory disease and those with co-existing diseases and poor prognosis.

The research team reported its experience in using Rituxan in AAV patients refractory (unresponsive) to conventional therapy. It also conducted a systematic literature review of studies of Rituxan in remission induction in AAV.

This analysis comprised a review of medical records of 25 AAV patients — 21 with granulomatosis with polyangiitis (GPA) — treated with Rituxan following insufficient response to immunosuppressive medications between 2011 and 2015. (Rituxan, by Genentech, was approved to treat GPA by the U.S. Food and Drug Administration in 2011.)

Intravenous Rituxan (two weekly doses of 1,000 mg or 375 mg/m2 per week for four weeks) was given for a median of two courses, with 24 months of follow-up. All 25 patients received concurrent treatment with steroids, 19 with intravenous methylprednisolone and oral prednisolone, and six with oral prednisolone only. Treatment cycles were repeated every six months.

At six months, 72 percent of patients receiving Rituxan had achieved a complete remission. At one year, the rate was 88 percent. Only three patients experienced minor relapses.

Infections were the most common adverse events. Two patients died due to refractory disease.

The literature review of Rituxan use included studies published until June 2017. A total of 56 studies involving 1,422 patients, most with refractory or relapsing AAV, were analyzed.

Concomitant immunosuppressives were given to 50 percent of these patients. This finding highlights the uncertain benefit of adding immunosuppressives, the team observed. The studies also had a large variability regarding AAV characteristics, endpoints, and Rituxan treatment protocol, which hampered generalization of findings.

Importantly, most reports showed complete or partial remission rates higher than 80 percent. The worst response – 37.5 percent – was in patients with granulomatous lesions (chronic inflammation). Although this result matches previous findings, other studies reported conflicting results.

“These conflicting results indicate the need for further studies to better understand the value of [Rituxan] in treating granulomatous lesions especially in refractory patients,” the researchers wrote.

The relapse rate was 30 percent. The most frequent adverse events were infections and infusion reactions.

Overall, “our experience with [Rituxan] in refractory AAV is in line with the literature in terms of efficacy and safety,” the team wrote.

“We still have few data on the long-term outcome of this treatment and on its efficacy on individual organ manifestations. In addition, more data on different patient populations are needed that would lead to the development of consensus on endpoints, outcome measures and treatment strategies,” the researchers concluded.