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Table of Contents   
CASE REPORT
Year : 2017  |  Volume : 12  |  Issue : 4  |  Page : 294-297
Rituximab treatment in patients with systemic sclerosis and interstitial lung disease


Department of Medical Specialties, Rheumatology Section, King Fahad Medical City, Riyadh, KSA

Date of Submission23-Jan-2017
Date of Acceptance15-May-2017
Date of Web Publication10-Oct-2017

Correspondence Address:
Ibrahim Abdulrazag Al-Homood
Department of Medical Specialties, Rheumatology Section, King Fahad Medical City, P. O. Box: 59046, Riyadh 11525
KSA
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DOI: 10.4103/atm.ATM_30_17

PMID: 29118864

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   Abstract 

There is increasing interest in rituximab (RTX) as an alternative to cyclophosphamide for the treatment of interstitial lung diseases (ILDs) associated with systemic sclerosis (SSc). However, no report has addressed its efficacy in Saudi patients with SSc-ILD. To assess the efficacy of RTX treatment in Saudi patients with SSc-ILD, hospital records were reviewed between 2013 and 2016. Four female patients received at least 4 cycles of RTX (I cycle, consisting of two infusions of 1000 mg 2 weeks apart). Pulmonary function tests (PFTs) and chest high-resolution computed tomography (HRCT) were performed before and after treatment to assess the response. HRCT revealed improvement in one patient, stable disease in two patients, and worsening in one patient. Moreover, RTX prevented the further decline of forced vital capacity significantly in PFT. These results provide further evidence that RTX is an effective treatment for SSc-ILD.


Keywords: Rituximab, systemic sclerosis, interstitial lung disease, high-resolution computed tomography


How to cite this article:
Mohammed AA, Alshihre A, Al-Homood IA. Rituximab treatment in patients with systemic sclerosis and interstitial lung disease. Ann Thorac Med 2017;12:294-7

How to cite this URL:
Mohammed AA, Alshihre A, Al-Homood IA. Rituximab treatment in patients with systemic sclerosis and interstitial lung disease. Ann Thorac Med [serial online] 2017 [cited 2020 Jan 20];12:294-7. Available from: http://www.thoracicmedicine.org/text.asp?2017/12/4/294/216293


Systemic sclerosis (SSc) is a multisystem autoimmune disease. Pulmonary manifestations are common, occurring in more than 80% of patients with SSc, resulting in a significant morbidity and mortality.[1] Interstitial lung disease (ILD) represents the most frequent pulmonary manifestation in SSc and more than 40% of patients showed restrictive changes in pulmonary function test (PFT).

PFT is frequently used to assess lung involvement in SSc, and an abnormal forced vital capacity (FVC) has been reported as a predictor for progression to end-stage lung disease.[2] Moreover, a lower FVC at the time of diagnosis is associated with higher mortality.[3]

Treatments for SSc-associated ILD (SSc-ILD) have mainly relied on nonspecific immunosuppression in the form of cyclophosphamide or mycophenolate.[4],[5]

Recently, few reports have suggested that rituximab (RTX), a chimeric monoclonal anti-CD20 antibody, may be an effective treatment option for SSc-related ILD.[6],[7]

The aim of our study was to evaluate the effect of RTX on Saudi patients with SSc-ILD.


   Methods Top


The current study included four patients with SSc-ILD, who attended Rheumatology Outpatient Clinic between 2013 and 2016 at King Fahad Medical City. All patients satisfied the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2013 criteria for SSc classification.[8]

Patients' records were reviewed. The following serological markers were detected by means of standard techniques, including anti-nuclear antibody (ANA), anti-Scl-70, PFT, high-resolution computed tomography (HRCT) as well as upper gastrointestinal endoscopy done for all patients [Table 1]. PFT measurements were done in the same respiratory laboratory. FVC was considered improved if there is <10% increment from the baseline.
Table 1: Patients' characteristics

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HRCTs were reported by an expert radiologist, who had no knowledge about the patient's status. Local research ethics committee approval was obtained for retrospective review of patients' records.


   Results Top


All patients were females, with positive ANA and anti-Scl-70, with mean disease duration of 7.25 years [Table 1]. ILD was detected in all patients. All patients received at least 4 cycles of RTX (1 g at day 0 and day 14 every 6 months). PFT and HRCT were done at baseline and after RTX, except one patient who lost follow-up. Patients were assessed following RTX by HRCT and PFT 6 months after the fourth cycle of RTX.

Statistical analysis

All patients had PFT before RTX treatment, with a mean ± SD of FVC of 63.4 ± 12.7. Following RTX, we observed improvement in FVC with a mean ± SD of 74.5 ± 6.8. HRCTs also improved in three out of four patients. In one patient (patient 1), PFT did not appear to change following treatment, but HRCT was worsening [Table 2].
Table 2: High-resolution computed tomography and pulmonary function test before and after rituximab

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   Discussion Top


SSc is frequently complicated by ILD that often has a poor prognosis.[9] Cyclophosphamide has been used for the treatment of SSc-ILD but its efficacy seems to be not sustained,[10] and it is not suitable for every patient, because of its side effects. Therefore, more effective treatment with fewer adverse effects is needed such as RTX.[6],[7],[11] Data from experimental studies suggest that B-cells have a significant role in the process of fibrosis supporting the idea of using B-cell-depleting agents such as RTX as a potential therapeutic approach in SSc.[12],[13]

As far as we know, we herein report the first retrospective study investigating four Saudi patients with SSc-ILD, showing that RTX treatment prevented the further decline of FVC significantly in PFTs of patients with SSc-ILD. Our findings are consistent with the results of previous studies [14],[15],[16] showing a possible role of RTX inpatients with SSc-ILD.

As ethnicity has been reported to affect the responsiveness to therapy,[17] further research in different populations is necessary to identify the effectiveness of RTX in SSc-ILD patients. This study highlights the effectiveness of RTX treatment in Saudi SSc-ILD patients. However, it is important to collect more cases and confirm the efficacy and safety of RTX therapy in Saudi patients.

In our study, HRCT revealed improvement in one patient [Figure 1], stable disease changes in two patients, and worsening in one patient, which is likely to be due to advance fibrosis (honeycombing appearance) at baseline and the presence of bronchiectasis; however, this worsening was not associated with deterioration in PFT.
Figure 1: (a) High-resolution computed tomography for a patient before rituximab. (b) High-resolution computed tomography for the same patient after rituximab

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In this study, a favorable response was demonstrated following RTX in the treatment of SSc-ILD. Nevertheless, administration of RTX to patients with autoimmune diseases might induce or lead to worsening of ILD.[18],[19]

Our study has its limitations. It is a retrospective study, with the possibility of data loss and the lack of a control group. It also has a small number of patients and different patient characteristics in terms of disease duration and severity. Therefore, a large randomized controlled trial is needed for further exploration of RTX efficacy in the treatment of SSc-ILD.

To our knowledge, this is the first study reporting the effectiveness of RTX in Saudi patients with SSc-ILD.


   Conclusion Top


RTX may improve SSc-ILD. Taking into consideration the limitations of our study, definite conclusions may not be reached. Nevertheless, our data could be an approach for multicenter studies to determine the effect of RTX in the treatment of SSc-ILD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G, et al. Systemic sclerosis: Demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 2002;81:139-53.  Back to cited text no. 1
    
2.
Morgan C, Knight C, Lunt M, Black CM, Silman AJ. Predictors of end stage lung disease in a cohort of patients with scleroderma. Ann Rheum Dis 2003;62:146-50.  Back to cited text no. 2
    
3.
Bouros D, Wells AU, Nicholson AG, Colby TV, Polychronopoulos V, Pantelidis P, et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 2002;165:1581-6.  Back to cited text no. 3
    
4.
Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006;354:2655-66.  Back to cited text no. 4
    
5.
Liossis SN, Bounas A, Andonopoulos AP. Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology (Oxford) 2006;45:1005-8.  Back to cited text no. 5
    
6.
Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Paliogianni F, Sirinian C, et al. Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol 2012;30 2 Suppl 71:S17-22.  Back to cited text no. 6
    
7.
Jordan S, Distler JH, Maurer B, Huscher D, van Laar JM, Allanore Y, et al. Effects and safety of rituximab in systemic sclerosis: An analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015;74:1188-94.  Back to cited text no. 7
    
8.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013;65:2737-47.  Back to cited text no. 8
    
9.
Chang B, Wigley FM, White B, Wise RA. Scleroderma patients with combined pulmonary hypertension and interstitial lung disease. J Rheumatol 2003;30:2398-405.  Back to cited text no. 9
    
10.
Wells AU, Denton CP. Interstitial lung disease in connective tissue disease – Mechanisms and management. Nat Rev Rheumatol 2014;10:728-39.  Back to cited text no. 10
    
11.
McQueen FM, Solanki K. Rituximab in diffuse cutaneous systemic sclerosis: Should we be using it today? Rheumatology (Oxford) 2015;54:757-67.  Back to cited text no. 11
    
12.
Fujimoto M, Sato S. B lymphocytes and systemic sclerosis. Curr Opin Rheumatol 2005;17:746-51.  Back to cited text no. 12
    
13.
Wollheim FA. Is rituximab a potential new therapy in systemic sclerosis? New evidence indicates the presence of CD20-positive B-lymphocytes in scleroderma skin. J Clin Rheumatol 2004;10:155.  Back to cited text no. 13
    
14.
Lepri G, Avouac J, Airò P, Anguita Santos F, Bellando-Randone S, Blagojevic J, et al. Effects of rituximab in connective tissue disorders related interstitial lung disease. Clin Exp Rheumatol 2016;34 Suppl 100:181-5.  Back to cited text no. 14
    
15.
Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, et al. A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum 2017;46:625-31.  Back to cited text no. 15
    
16.
Ebata S, Yoshizaki A, Fukasawa T, Nakamura K, Yamashita T, Miura S, et al. Unprecedented success of rituximab therapy for prednisolone- and immunosuppressant-resistant systemic sclerosis-associated interstitial lung disease. Scand J Rheumatol 2017;46:247-52.  Back to cited text no. 16
    
17.
Watson CT, Steinberg KM, Huddleston J, Warren RL, Malig M, Schein J, et al. Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. Am J Hum Genet 2013;92:530-46.  Back to cited text no. 17
    
18.
Calderazzo M, Rende P, Gambardella P, De Sarro G, Gallelli L. A case of interstitial lung disease probably related to rituximab treatment. Drug Saf Case Rep 2015;2:8.  Back to cited text no. 18
    
19.
Nakamura K, Yoshizaki A, Takahashi T, Saigusa R, Taniguchi T, Asano Y, et al. The first case report of fatal acute pulmonary dysfunction in a systemic sclerosis patient treated with rituximab. Scand J Rheumatol 2016;45:249-50.  Back to cited text no. 19
    


    Figures

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    Tables

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