Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

Low-dose rituximab as an adjuvant therapy in pemphigus.

BACKGROUND: Pemphigus is a chronic autoimmune blistering disease where systemic steroids and immunosuppressants are the mainstay of therapy, but long-term treatment with these agents is associated with many side effects. Rituximab, a chimeric monoclonal anti-CD20 antibody, in low doses has shown efficacy as an adjuvant to reduce the dose of steroids. AIM: To study the clinical efficacy and safety of low-dose rituximab as an adjuvant therapy in pemphigus. METHODS: Fifty patients with extensive pemphigus were selected, who either had recalcitrant pemphigus, were steroid dependent, had relapsed after pulse therapy, had anti-desmoglein levels >20, had contraindications to conventional treatment or wanted to avoid conventional treatment and its side effects. Two doses of rituximab (500 mg) were given 2 weeks apart and patients were regularly followed up every 2 weeks for 3 months and then monthly upto 2 years. Complete blood counts, liver function tests, renal function tests, skin biopsy, direct immunofluorescence and desmoglein levels were checked before and after rituximab administration. Pre-rituximab chest X-ray and electrocardiograph were also obtained. RESULTS: At 3 months, 41 (82%) patients showed complete remission. Nine (18%) patients had partial remission. After 6-12 months, 20 (40% of enrolled patients) continued to be in remission and were off all systemic therapy and the remaining 19 (38%) were continuing to take low doses of steroids with or without other adjuvant immunosuppressants and 2 (4%) had to be given another 2 doses of rituximab and subsequently could be managed with low-dose steroids. Of the 9 patients in partial remission at 3 months, after 6-12 months 5 (10% of the total) were completely off treatment and went into complete remission and 4 (8%) were on additional treatment out of which 2 (4%) had to be given 2 additional doses of rituximab and were in partial remission with low-dose therapy at the end of 12 months. One patient developed urticaria as a side effect. Another developed herpes zoster. CONCLUSION: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

Clinical efficacy of rituximab in the treatment of pemphigus: A retrospective study.

BACKGROUND: Pulsed corticosteroids have been used successfully for the management of pemphigus. However, prolonged use of glucocorticoids may be associated with adverse effects and some patients show a poor response to conventional therapy. Biologics have shown a promising role in such cases; however, there is limited data from the Indian subcontinent. OBJECTIVE: The primary objective was to assess the efficacy and adverse effects of rituximab in pemphigus. The secondary objective was to measure the cumulative doses of corticosteroids required for these patients. METHODS: We undertook a retrospective review of records of 25 pemphigus patients (pemphigus vulgaris: 21, pemphigus foliaceus: 4) who had received rituximab infusion (rheumatoid arthritis protocol in 21 patients, modified in 4). Oral prednisolone was administered in dosages up to 0.5 mg/kg of body weight and tapered over the next 3-4 months according to the disease activity. However, other immunosuppressive agents such as cyclophosphamide and azathioprine were continued for one year after clinical remission was achieved. RESULTS: Complete remission was observed in 22 (88%) patients. The mean time to disease control and complete remission was 1.10 and 4.36 months, respectively. Four (16%) patients experienced relapse after a mean duration of 11.75 months. The mean total dose of oral steroids administered was equivalent to 3535.64 mg of prednisolone. Exacerbation of disease was noted in two patients after the first dose of rituximab and infectious complications, pneumonia and cellulitis, developed in one patient each. LIMITATIONS: A small sample size, the retrospective nature of the study and unavailability of follow-up anti-desmoglein autoantibodies levels were limitations. CONCLUSION: Rituximab is an effective agent in the treatment of pemphigus. The use of rituximab enabled use of a lower initial dose of oral prednisolone in pemphigus and hence reduced its total cumulative dose. Severe side effects were rare.