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Systemic sclerosis (SSc) treated with rituximab (Rituxan) was associated with improvements in skin, but not lung, disease manifestations, a prospective study conducted by the European Scleroderma Trials and Research (EUSTAR) network found.

Among 254 patients with SSc followed for a median of 2 years, the modified Rodnan Skin Score declined from a mean of 22.1 to 14.1 for those receiving rituximab compared with a decrease from 21.1 to 16.2 for controls (P<0.0001), according to Muriel Elhai, MD, of Paris Descartes University in France, and colleagues.

Lung fibrosis remained stable but did not improve during the B-cell depleting treatment. For example, forced vital capacity (FVC) was 76.3% of predicted at baseline and 77.7% at last follow-up in the rituximab group, which was similar to a change from 79.1% to 80.7% in those not given rituximab, the researchers reported online in .

Interstitial lung disease remains the most common cause of death in SSc, and treatment options for it are few.

Despite the lack of improvement in lung fibrosis seen in this study, the benefits for cutaneous manifestations merit consideration. "Indeed, worsening in modified Rodnan Skin Score is associated with higher mortality and worsening of internal organ involvement. Conversely, improvement of the skin score is predictive of favorable outcomes, including better survival," Elhai and colleagues noted.

The study also highlights the differences in disease evolution and response to treatment for lung and skin disease in SSc, as was previously seen in a (Actemra) in which benefits were seen for lung manifestations but not skin.

Accordingly, combination therapy has the potential for a better impact on SSc outcomes, the researchers said.

Case reports and small series had suggested that targeting B cells with rituximab might be beneficial, and from EUSTAR that included 63 patients showed skin improvements and stabilization of lung function, but was limited by only 6 months of follow-up.

Therefore, to examine the efficacy and safety of rituximab in a larger cohort and with longer follow-up, Elhai and colleagues identified 254 patients in the EUSTAR database who had been treated with the drug through 2017. Median age was 51 years in this cohort, of which 71% were women. Additionally, 64% had the diffuse cutaneous subtype of SSc, and 71% had lung fibrosis.

Propensity scores were calculated to compare rituximab recipients with controls, a group of 9,575 patients in the database who had not received the drug.

Treatments prior to rituximab included disease-modifying antirheumatic drugs (DMARDs) in 32.5% of cases, biologics in 9.5%, and cyclophosphamide in 9.1%.

According to the records in the database, the reasons for prescribing B-cell depleting therapy were lung involvement in 58% of cases, cutaneous disease in 32%, and musculoskeletal manifestations in the remainder.

Concomitant medications included corticosteroids in two-thirds of patients, DMARDs in more than half, and mycophenolate mofetil (CellCept), azathioprine, and cyclophosphamide in smaller numbers.

Among rituximab-treated patients whose baseline modified Rodnan Skin Score was 10 or higher, there was a decrease from 21.2 to 13.4 compared with a decline from 20.4 to 16 among controls (P<0.0001).

Overall, the rituximab-treated patients were significantly more likely to experience an improvement in skin fibrosis, with an odds ratio of 2.79 (95% CI 1.47-5.32), compared with controls.

As with FVC, diffusing capacity of lung for carbon monoxide was stable in both the rituximab group, being 54.4% predicted at baseline and 55.5% at last follow-up, and among controls, at 55.6% and 54.7%, respectively.

In a secondary analysis, a trend for improvement in FVC was seen among patients on rituximab plus mycophenolate, who had a change from baseline of 5.22% (95% CI 0.83-9.62) compared with a change of 3% (95% CI 0.66-5.35) for rituximab alone.

Additional analyses found improvements in musculoskeletal symptoms such as Disease Activity Scores in 28 joints (decreasing from 4.68 at baseline to 2.60 at last follow-up, P<0.0001) and in markers of inflammation such as C-reactive protein levels (which declined from 11.5 to 6.7 mg/L, P<0.0001).

In addition, patients were twice as likely as controls to be able to decrease or stop taking steroids (OR 2.34, 95% CI 1.56-3.53, P<0.0001). "This is of major importance, since steroids' cumulative dose increases the risk of subclinical/clinical atherosclerosis and scleroderma renal crisis in SSc," the researchers said.

With regard to safety, 17% of the rituximab group reported minor adverse events, 14% had serious adverse events, and 9% discontinued treatment. Six patients died, with two being possibly related to the treatment (respiratory insufficiency associated with lung cancer).

A limitation of the study was its open-label observational design.

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