Safe Use of Rituximab in an Elderly Patient With Rheumatoid Arthritis and Severe Heart Failure
Heart failure (HF), as a common comorbidity of rheumatoid arthritis (RA),1 limits treatment options after disease-modifying antirheumatic drugs have failed. We present our successful use of rituximab (dose, 2 × 500 mg) to achieve symptom remission of RA, without aggravation of HF status in a 76-year-old man. Further studies are needed to evaluate the long-term safety and effectiveness of rituximab for the treatment of patients with RA who have severe HF.
Disease-modifying antirheumatic drugs used included hydroxychloroquine and sulfasalazine, from January 24, 2011, to July 31, 2011; addition of methotrexate on March 14, 2011; and replacement of hydroxychloroquine and sulfasalazine by leflunomide on August 1, 2011. Because of liver toxicity, leflunomide was discontinued, and tacrolimus treatment was initiated on January 8, 2014.
On admission, the Disease Activity Score in 28 Joints was 6.54: tender joint count, 17; swollen joint count, 10; visual analog scale pain score, 60/100 mm; and erythrocyte sedimentation rate, 36 mm/h. Salient laboratory findings included a white blood cell count of 10,370/μL and high-sensitivity C-reactive protein level of 34.72 mg/L. On echocardiography, the ejection fraction was 25%, with an ischemic myopathy of the left ventricle. Radiographic examination revealed erosive changes with multiple subchondral cysts of the carpal bones and diffuse joint space narrowing of the radiocarpal and intercarpal joints. Internal fixation of the left radius, carpal, and third metacarpal bone was observable (Fig. 1).
The dose of methotrexate was increased from 12.5 mg/wk to 15 mg/wk for symptom control, but discontinued at 1 week because of deteriorating renal function. In the absence of RA treatment guidelines (March 2015), our decision to use rituximab was based on the following clinical evidence: a case report of the combined use of rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) to treat non-Hodgkin lymphoma, with no evidence of HF aggravation,2 and the comparable effectiveness and safety of 2 × 500-mg and 2 × 1000-mg doses of rituximab.3 Considering the advanced age of our patient and the presence of HF and decreased renal function, treatment consisted of two 500-mg doses of rituximab, by intravenous infusion, at a 2-week interval, combined with 100 mg of methylprednisolone, as per prescribing information.4 Pain control was achieved, with only facial flushing as an adverse effect, and the patient was discharged the following week.
At 4 months posttreatment, the Disease Activity Score in 28 Joints was 3.28: tender joint count, 1; swollen joint count, 11; VAS pain score, 20/100 mm; and erythrocyte sedimentation rate, 19 mm/h. Symptom management was maintained using methotrexate (7.5 mg/wk) and hydroxychloroquine (100 mg/d). Two subsequent flare-ups were managed by a repeated cycle of rituximab, with no adverse effects and a stable ejection fraction maintained after each cycle, with stable RA status at the 2-year follow-up (Fig. 2).
Although rituximab was previously contraindicated because of concerns of HF aggravation,5 there was no effect of our protocol on our patient's HF status. Rituximab was newly listed as a treatment option for the patient with RA and HF in the 2015 American College of Rheumatology guidelines.6 Moreover, in April 2016, the prescribing information for rituximab was revised, and the limitation on its use was removed.4 We hope that our case will foster enhanced discussion regarding the use of rituximab for the treatment of patients with RA, regardless of HF status.