We examined research published up to January 2014 on the effect of rituximab for people with rheumatoid arthritis. From eight studies evaluating 2720 people with rheumatoid arthritis, we found that rituximab probably:
- improved pain, function and other symptoms;
- reduced disease activity;
- reduced joint damage as seen on the x-ray.
We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects are infusion reactions, vascular disorders, and infections.
What is rheumatoid arthritis and what is rituximab?
When you have rheumatoid arthritis, your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff, and painful. There is no cure for rheumatoid arthritis at present, so the treatments aim to relieve pain and improve your ability to move.
Rituximab works by depleting the levels of B-cells, a type of immune cell in the body that causes swelling and joint damage in people who have rheumatoid arthritis. Rituximab is given intravenously. Rituximab is of great interest to rheumatoid arthritis patients based on improvements in symptoms and radiographic progression, and the low rate of short-term side effects.
What happens to people with rheumatoid arthritis who are given rituximab plus methotrexate?
ACR 50 (number of tender or swollen joints, pain, and disability)
- 21 more people out of 100 experienced improvement in their symptoms after 6 months with rituximab plus methotrexate compared to methotrexate alone (21% absolute improvement)*.
- 29 people out of 100 experienced improvement with rituximab plus methotrexate compared to 9 out of 100 who took methotrexate alone.
Disease activity
- 11 more people out of 100 achieved remission of their rheumatoid arthritis after 1 year with rituximab plus methotrexate compared to methotrexate alone (11% absolute improvement).
- 22 people out of 100 on rituximab plus methotrexate achieved remission compared to 11 out of 100 who took methotrexate alone.
Physical function
- 24 more people out of 100 achieved a meaningful improvement in their physical function after 2 years with rituximab plus methotrexate compared to methotrexate alone (24% absolute improvement).
- 85 people out of 100 on rituximab plus methotrexate achieved a meaningful improvement in their physical function compared to 61 out of 100 who took methotrexate alone.
X-rays of the joints
- 19 more people out of 100 had no damage to their joints after 2 years with rituximab plus methotrexate compared to methotrexate alone (19% absolute improvement)*.
- 57 people out of 100 on rituximab plus methotrexate had no damage to their joints compared to 39 out of 100 who took methotrexate alone.
Quality of life - physical component (general health, pain, and ability to perform physical activities)
- 34 more people out of 100 perceived their general health, pain, and ability to perform physical activities better after 6 to 12 months with rituximab plus methotrexate compared to methotrexate alone (34% absolute improvement)*.
- 70 people out of 100 who took rituximab plus methotrexate perceived their general health, pain, and ability to perform physical activities to be better compared to 36 out of 100 who took methotrexate alone.
Quality of life - mental component
- 13 more people out of 100 perceived their mental well-being better after 6 to 12 months with rituximab plus methotrexate compared to methotrexate alone (13% absolute improvement).
- 48 people out of 100 who took rituximab plus methotrexate perceived their mental well-being to be better compared to 35 out of 100 who took methotrexate alone.
Discontinuations due to adverse events
- 2 less people out of 100 discontinued rituximab plus methotrexate due to side effects after 2 years compared to methotrexate alone (-2% absolute withdrawals).
- 3 people out of 100 who took rituximab plus methotrexate discontinued methotrexate due to side effects compared to 5 out of 100 who took a placebo.
Serious adverse events
- 4 less people out of 100 experienced serious side effects after 2 years with rituximab plus methotrexate compared to methotrexate alone (-4% absolute harms).
- 13 people out of 100 who took rituximab plus methotrexate had side effects compared to 17 out of 100 who took methotrexate alone.
*1% unit difference due to rounding.
Evidence from eight studies suggests that rituximab (two 1000 mg doses) in combination with methotrexate is significantly more efficacious than methotrexate alone for improving the symptoms of RA and preventing disease progression.
Rituximab is a selective, B-cell depleting, biologic agent for treating refractory rheumatoid arthritis (RA). It is a chimeric monoclonal antibody targeted against CD 20 that is promoted as therapy for patients who fail to respond to other biologics. There is evidence to suggest that rituximab is effective and well tolerated when used in combination with methotrexate for RA.
To evaluate the benefits and harms of rituximab for the treatment of RA.
We conducted a search (until January 2014) in electronic databases (The Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science), clinical trials registries, and websites of regulatory agencies. Reference lists from comprehensive reviews were also screened.
All controlled trials comparing treatment with rituximab as monotherapy or in combination with any disease modifying anti-rheumatic drug (DMARD) (traditional or biologic) versus placebo or other DMARD (traditional or biologic) in adult patients with active RA.
Two review authors independently assessed the risk of bias and abstracted data from each study.
We included eight studies with 2720 patients. For six studies selection bias could not be evaluated and two studies were considered to have low risk of bias. The level of evidence ranged from low to high, but was rated as moderate for most outcomes. We have prioritised reporting of rituximab (two 1000 mg doses) in combination with methotrexate since this is the approved dose and most commonly used combination. We also reported data on other combinations and doses as supplementary information in the results section of the review.
American College of Rheumatology (ACR) 50 response rates were statistically significantly improved with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate alone at 24 to 104 weeks. The RR for achieving an ACR 50 at 24 weeks was 3.3 (95% CI 2.3 to 4.6); 29% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved the ACR 50 compared to 9% of controls. The absolute treatment benefit (ATB) was 21% (95% CI 16% to 25%) with a number needed to treat (NNT) of 6 (95% CI 4 to 9).
At 52 weeks, the RR for achieving clinical remission (Disease Activity Score (DAS) 28 joints < 2.6) with rituximab (two 1000 mg doses) in combination with methotrexate compared with methotrexate monotherapy was 2.4 (95% CI 1.7 to 3.5); 22% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate achieved clinical remission compared to 11% of controls. The ATB was 11% (95% CI 2% to 20%) with a NNT of 7 (95% CI 4 to 13).
At 24 weeks, the RR for achieving a clinically meaningful improvement (CMI) in the Health Assessment Questionnaire (HAQ) (> 0.22) for patients receiving rituximab combined with methotrexate compared to patients on methotrexate alone was 1.6 (95% CI 1.2 to 2.1). The ATB was 24% (95% CI 12% to 36%) with an NNT of 5 (95% CI 3 to 13). At 104 weeks, the RR for achieving a CMI in HAQ (> 0.22) was 1.4 (95% CI 1.3 to 1.6). The ATB was 24% (95% CI 16% to 31%) with a NNT of 5 (95% CI 3 to 7).
At 24 weeks, the RR for preventing radiographic progression in patients receiving rituximab (two 1000 mg doses) in combination with methotrexate was 1.2 (95% CI 1.0 to 1.4) compared to methotrexate alone; 70% of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate had no radiographic progression compared to 59% of controls. The ATB was 11% (95% CI 2% to 19%) and the NNT was 10 (95% CI 5 to 57). Similar benefits were observed at 52 to 56 weeks and 104 weeks.
Statistically significantly more patients achieved a CMI on the physical and mental components of the quality of life, measured by the Short Form (SF)-36, in the rituximab (two 1000 mg doses) in combination with methotrexate-treated group compared with methotrexate alone at 24 to 52 weeks (RR 2.0, 95% CI 1.1 to 3.4; NNT 4, 95% CI 3 to 8 and RR 1.4, 95% CI 1.1 to 1.9; NNT 8, 95% CI 5 to 19, respectively); 34 and 13 more patients out of 100 showed an improvement in the physical component of the quality of life measure compared to methotrexate alone (95% CI 5% to 84%; 95% CI 7% to 8%, respectively).
There was no evidence of a statistically significant difference in the rates of withdrawals because of adverse events or for other reasons (that is, withdrawal of consent, violation, administrative, failure to return) in either group. However, statistically significantly more people receiving the control drug withdrew from the study compared to those receiving rituximab (two 1000 mg doses) in combination with methotrexate at all times (RR 0.40, 95% CI 0.32 to 0.50; RR 0.61, 95% CI 0.40 to 0.91; RR 0.48, 95% CI 0.28 to 0.82; RR 0.58, 95% CI 0.45 to 0.75, respectively). At 104 weeks, 37% withdrew from the control group and 20% withdrew from the rituximab (two 1000 mg doses) in combination with methotrexate group. The absolute risk difference (ARD) was -20% (95% CI -34% to -5%) with a number needed to harm (NNH) of 7 (95% CI 5 to 11).
A greater proportion of patients receiving rituximab (two 1000 mg doses) in combination with methotrexate developed adverse events after their first infusion compared to those receiving methotrexate monotherapy and placebo infusions (RR 1.6, 95% CI 1.3 to 1.9); 26% of those taking rituximab plus methotrexate reported more events associated with their first infusion compared to 16% of those on the control regimen with an ARD of 9% (95% CI 5% to 13%) and a NNH of 11 (95% CI 21 to 8). However, no statistically significant differences were noted in the rates of serious adverse events.