The PGA scores indicated that patients in the 3M group were significantly more likely to report less severe disease vs the R group (P=.008)(eTable 3).
Multivariate Analysis—Effect of the patient characteristics and some disease features on indices of QOL was evaluated using the multiple linear regression model. eTable 4 shows the P values of those analyses.
COMMENT
Pemphigus is a chronic disabling disease with notable QOL impairment due to disease burden as well as the need for long-term use of immunosuppressive agents during the disease course. To study the effect of RTX on QOL of patients with pemphigus, we compared 2 sets of patients. Prior studies have shown that clinically significant effects of RTX take 4 to 12 weeks to appear.19,20 Therefore, we selected patients who received RTX 3 months earlier to measure their HRQOL indices and compare them with patients who had received RTX in the last 2 weeks as a control group to investigate the effect of RTX intrinsically, as this was the focus of this study.
In our study, one of the research tools was the DLQI. Healthy patients typically have an average score of 0.5.21 The mean DLQI score of the patients in R group was 12.31, which was similar to prior analysis8 and reflects a substantial burden of disease comparable to atopic dermatitis and psoriasis.21,22 In patients in the 3M group, the mean DLQI score was lower than the R group (6.96 vs 12.31), indicating a significant (P=.005) and clinically meaningful improvement in QOL of patients due to the dramatic therapeutic effect of RTX. However, this score indicated a moderate effect on HRQOL, even in the context of clinical improvement due to RTX treatment, which may reflect that the short duration of treatment in the 3M group was a limitation of this study. Although the 12-week treatment duration was comparable with other studies19,20 and major differences in objective measures of treatment efficacy were found in PDAI as well as anti-DSG1 and anti-DSG3 values, longer treatment duration may be needed for a more comprehensive assessment of the benefit of RTX on HRQOL indices in patients with pemphigus.
Based on results of the SF-36 questionnaire, PCS and MCS scores were not substantially impaired in the R group considering the fact that a mean score of 50 has been articulated as a normative value for all scales.23 These data demonstrated the importance of using a dermatologic-specific instrument such as the DLQI instead of a general questionnaire to assess QOL in patients with pemphigus. However, better indices were reported with RTX treatment in the 3 SF-36 domains—role physical (P=.009), role emotional (P=.03), and general health perception (P=.03)—with the role physical showing the greatest magnitude of mean change (75.45 in the 3M group vs 53.04 in the R group). Notably, PCS was impaired to a greater extent than MCS in patients in the R group and showed a greater magnitude of improvement after 3 months of treatment. These results could be explained by the fact that MCS can be largely changed in diseases with a direct effect on the central nervous system.23
Our results also revealed that the dose of corticosteroid correlated to HRQOL of patients with pemphigus who recently received RTX therapy. Indeed, it is more likely that patients on lower-dose prednisolone have a higher QOL, especially on physical function and social function dimensions of SF-36. This finding is highly expectable by less severe disease due to RTX treatment and also lower potential dose-dependent adverse effects of long-term steroid therapy.
One of the most striking findings of this study was the correlation of location of lesions to QOL indices. We found that the mucocutaneous phenotype was significantly correlated to greater improvement in role emotional, role physical, and social functioning scores due to RTX treatment compared with cutaneous or mucosal types (P=.02, P=.025, and P=.017, respectively). Although mucosal involvement of the disease can be the most burdensome feature because of its large impact on essential activities such as eating and speaking, cutaneous lesions with unpleasant appearance and undesirable symptoms may have a similar impact on QOL. Therefore, having both mucosal and cutaneous lesions causes a worsened QOL and decreased treatment efficacy vs having only one area involved. This may explain the greater improvement in some QOL indices with RTX treatment.
Limitations—Given the cross-sectional design of this study in which patients were observed at a single time point during their treatment course, it is not possible to establish a clear cause-effect relationship between variables. Moreover, we did not evaluate the impact of RTX or prednisolone adverse effects on QOL. Therefore, further prospective studies with longer treatment durations may help to validate our findings. In addition, MCDs for DLQI and SF-36 in pemphigus need to be determined and validated in future studies.
CONCLUSION
The results of our study demonstrated that patients with pemphigus may benefit from taking RTX, not only in terms of clinical improvement of their disease measured by objective indices such as PDAI and anti-DSG1 and anti-DSG3 values but also in several domains that are important to patients, including physical and mental health status (SF-36), HRQOL (DLQI), and overall disease severity (PGA). Rituximab administration in patients with pemphigus can lead to rapid and significant improvement in HRQOL as well as patient- and physician-assessed measures. Its favorable safety profile along with its impact on patients’ daily lives and mental health makes RTX a suitable treatment option for patients with pemphigus. Moreover, we recommend taking QOL indices into account while evaluating the efficacy of new medications to improve our insight into the patient experience and provide better patient adherence to treatment, which is an important issue for optimal control of chronic disorders.