Likewise, the overall treatment satisfaction rating(scale range: 1–7), significantly improved from a mean of 4.8, with injectabletherapies, to a mean of 6.3 after 1 year of rituximab treatment, which remains sustainedby 2 years.
There was no significant alteration in scores for the patient-perceived impact of disease, fatigue ordisease progression 13. In a comparative study, a total of 461 patients fromthe Swedish MS registry in the rituximab arm and 922 patients from the IFN-?/GAarm in RRMS were compared 14. The results were indicative of a significant reduction in Annualized Relapse Rate (ARR)associated with rituximab use. In addition, rituximab was associated with an87% decrease in the relapse rate and a discontinuation rate reduction by 85%relative to IFN-?/GA. When examined at 12 and 24months, Expanded Disability Status Scale (EDSS) was significantly regressed (improved) from baseline in the rituximabgroup.
In contrast, the OLYMPUS trial which is a phase II/III trial, enrolled439 patients with PPMS and followed them for 96 weeks, failed to show anyreduction in disease progression during follow up period 15. However, whenlooking at subgroups of patients younger than 50 yearsor regarding the Gadolinium-enhanced lesions at baseline, a significant effect was detected 15. An observational studyof three SPMS patients who were treated with rituximab for at least 15months showed that EDSS score stabilized in all patients after a dramatic increaseover the previous year’s 16. Finally, a retrospective observational report of822 Swedish patients with MS, including 557 RRMS, 67 PPMS and 198 SPMS who weretreated with intravenous rituximab (500 or 1000 mg every 6 to 12 months) for amean duration of 22 months showed that patients with RRMS had a low mean yearlyrelapse rate (0.04) during rituximab treatment and their median disabilitystatus remained unchanged. Patients with PPMS had a low mean annualized relapserate (0.
015) during rituximab therapy and their median disability status increased.Patients with SPMS had a low mean annualized relapse rate (0.038) and theirmedian disability status increased. Infections were the most common noninfusion-related adverse event of rituximab 17.According to available studies, rituximab might bean effective treatment option in patients with RRMS and possibly in a subset ofPPMS patients, but due to licensing issues the study was not further conducted for the treatment of MS 18, 19. These results suggest that although several research has been carried out, decisions making regarding the use ofrituximab in MS based on available evidence isdifficult at the moment and especially when there are requests for off label uses. Particularly in our study, mostpatients who received rituximab for the treatmentof MS, were suffering from SPMS on which available studies are limited.
Although some studies suggest that rituximab cancontribute to the improvement of skin and articular involvement, and possiblythe pulmonary fibrosis of systemic sclerosis (SSc), most of these studies arecase reports or open label studies 20-34. SSc is a connectivetissue disorder with a chronic and frequently progressive course. Patients with SSc canbe roughly grouped into diffuse cutaneous and limited cutaneous subsets regardingthe pattern of skin involvement,clinical and laboratory features. Recently, the European Scleroderma Trial andResearch (EUSTAR) cohort compared the two groups of rituximab treated anduntreated match–control SSc patients and demonstrated that improvement of skin?brosis could prevent worsening lung ?brosis.
These findings support theconcept of B cell inhibition in the treatment of SSc. Although, this study isthe largest case- control study available so far, and although it addsimportant aspects to rituximab and other B cell targeting therapies in generaland as a potential anti?brotic treatment strategy in SSc; this might not beconclusive as it is not a randomized controlled trial and couldn’t preciselyexplain the ef?cacy and relative safety of rituximab on skin and lung ?brosisin SSc as compared with placebo treatment 32. Similarly, Update of EULARrecommendations emphasizes on several (potential) drugs, including newpromising therapies that might be helpful in the management of patients withSSc that could not be included in these evidence-based recommendations due toinsufficient data at present 35.There are evidencethat rituximab treatment in patients with resistant idiopathic inflammatorymyopathies has some benefits 36. Idiopathic inflammatory myopathies (IIMs) are agroup of acquired, heterogeneous, systemic diseases of skeletal muscle,including adult Polymyositis (PM) and Dermatomyositis (DM), Juvenile DM (JDM)and PM (JPM), Anti-Synthetase Syndrome (ASS) and IBM. PMand DM are two major and discrete subtypes of IIMs which present withinvolvement of skeletal muscles, the skin and other organs 36, 37. B cellsplay a critical role in the initiation and progression of the immune responsewhich has been suggested to be involvedin the pathogenesis of myositis.
Considering the likelihood of pathogeneticrole of B cells in myositis, rituximab may have a role in the treatment ofmyositis in several studies 36. A large clinical trial Rituximab in Myositis (RIM), randomized 200 patients with refractorymyositis (76 with PM, 76 with DM and 48 with JDM) to receive different regimensof rituximab (two infusions at baseline or 8 weeks later).