Can Rituximab (rituximab) be used as maintenance therapy in systemic sclerosis?

Rituximab as Maintenance Therapy in Systemic Sclerosis

Rituximab can be used as maintenance therapy in systemic sclerosis, with evidence supporting sustained clinical benefit through repeated courses for both skin and lung manifestations, though this represents off-label use without formal FDA approval for this indication.

Evidence for Maintenance Therapy

The most recent and highest-quality evidence demonstrates that rituximab maintenance provides sustained improvement in systemic sclerosis:

• Two courses of rituximab (at baseline and 24 weeks) showed sustained improvement in modified Rodnan skin score (mRSS) through 48 weeks, with the rituximab-rituximab group achieving a mean improvement of -8.88 points from baseline 1
• Long-term follow-up data (median 96 weeks) confirmed that continued rituximab treatment maintains clinical response, with significant improvement in mRSS after 1 course (median change -7 points) and FVC% after 3 courses (median change +1.85%) that persisted throughout follow-up 2
• The 5-year retention rate for rituximab in systemic sclerosis was 59.9%, with clinical response being the most common reason for discontinuation (indicating successful treatment allowing cessation), not treatment failure 3

Recommended Maintenance Protocol

Based on the available evidence, the following approach is supported:

• Initial induction consists of rituximab 375 mg/m² IV once weekly for 4 consecutive weeks 1
• Maintenance dosing should be repeated every 24 weeks (6 months) using the same 4-week course regimen 1, 2
• Continue maintenance therapy for at least 48-96 weeks to achieve maximal benefit for both skin and lung manifestations 1, 2

Clinical Response Monitoring

High responders (≥9 point mRSS improvement) demonstrate greater decreases in serum IgG and IgA levels, with IgA reduction correlating significantly with mRSS improvement (r=0.64) 2. This provides an objective marker for treatment response.

Monitor the following parameters:

• mRSS assessment every 24 weeks to evaluate skin response 1
• FVC% and DLCO every 24 weeks to monitor lung function stability 4, 2
• Serum immunoglobulin levels (IgG, IgA, IgM) every 2-4 months during treatment, as decreases correlate with clinical response 2
• Complete blood count with differential every 2-4 months 5

Safety Profile During Maintenance

The long-term safety data support continued use:

• Overall adverse event rate is 10 per 100 patient-years, with most events being mild to moderate (71%) 6
• Serious adverse event rate is 3.2 per 100 patient-years 6
• Infection rate is 7.1 per 100 patient-years, with serious infections at 1.5 per 100 patient-years and no opportunistic infections reported 6
• Adverse events were the least common cause of rituximab discontinuation (3.1 per 100 patient-years), indicating favorable tolerability 3

Critical Monitoring Considerations

IgG levels typically decrease during treatment but remain within normal limits on average 6. However:

• Monitor for IgG levels below 3 g/L, which may warrant immunoglobulin supplementation 5
• Consider PJP prophylaxis if additional risk factors or low CD4 counts are present 5
• Low IgM at follow-up was associated with greater FVC% improvement (median change +7.2% vs +3.6%), suggesting this may be a marker of lung response 2

Predictors of Response

Anti-topoisomerase-I positivity is associated with better treatment persistence and lower treatment failure rates (sHR 0.2 for treatment failure) 3. Conversely, anti-centromere antibody positivity is associated with higher treatment failure rates (sHR 2.8) 3.

Duration of Maintenance

Clinical response was the most common reason for discontinuation (5.7 per 100 patient-years), occurring after a median disease duration that was shorter in responders 3. This suggests that:

• Maintenance can be continued as long as clinical benefit persists
• Discontinuation should be considered when sustained remission is achieved (typically after 48-96 weeks minimum)
• Close monitoring every 3-6 months after discontinuation is warranted to detect disease reactivation 7

Common Pitfalls to Avoid

• Do not discontinue prematurely: Lung function improvement may not be evident until after 3 courses (approximately 48 weeks) 2
• Do not ignore immunoglobulin monitoring: Hypogammaglobulinemia can develop and requires proactive management 6, 2
• Do not use fixed short-term protocols: The evidence supports extended maintenance beyond initial induction for sustained benefit 1, 2