Rituximab Utilization Evaluation with Focused on Available Evidence for Off-Labeled Indications
-
Maryam Farasatinasab
,
Sohrab Aghabeigi
,
Soodeh Ramezaninejad
,
Atefeh Amouzegar
,
Behrooz Ghanbari
,
Nashmin Pakdaman
,
Mohammad Reza Motamed
,
Simin Almasi
,
Nader Rezaie
,
Somayyeh Nasiripour
,
Forough Sabzghabaei
,
Ali Basi
Abstract
Objectives: To investigate the on-labeled and off-labeled indications of rituximab according to available evidence and the cost in our center.
Methods: This retrospective cross-sectional study was conducted between August 2016 and August 2017 at a teaching hospital affiliated to Iran University of Medical Sciences, Tehran, Iran. Patients’ demographic data and disease, indication for rituximab use, its dosage and treatment regimen and previous and concurrent treatments was assessed. The collected data were compared with the current criteria for the pattern of rituximab use. The last version of Lexicomp® acquired by Wolters Kluwer was used as the reference for on-labeled and off-labeled indications of the prescribed drug and its dosage. Level of evidences for applied indications and cost has also been evaluated.
Results: A total of 85 patients received rituximab during the study period. The most frequent reasons for rituximab prescription were: multiple sclerosis (50.58%), systemic sclerosis (10.58%), rheumatoid arthritis (7.05%) and Idiopathic inflammatory myopathies (4.70%). Rituximab was used in 8 (9.4%) cases according to on-labeled indications. There was level C evidence for rituximab use in off-labeled indications in 47 (55.29%) cases according to available evidences which accounts for the highest calculated cost.
Conclusion: Based on our results, rituximab was frequently administrated for off-labeled indications most of which are not supported by established levels of evidence. The total cost was higher for level C evidence indications of off labeled rituximab than for indications with a higher level of evidence (A and B). So, strong evidence is necessary for decision making regarding its effectiveness and its cost benefit.
1. http://www.wolterskluwerhealth.com/News/Pages/WoltersKluwerHealthtoAcquireLeadingGlobalDrugInformationProviderLexi-Comp.aspx
2. Danés I, Agustí A, Vallano A, et al. Available evidence and outcome of off-label use of rituximab in clinical practice. Eur J Clin Pharmacol 2013; 69(9):1689-99.
3. Van Allen EM, Miyake T, Gunn N, Behler CM, Kohlwes J. Off-label use of rituximab in a multipayer insurance system. J Oncol Pract 2011;7:76–79.
4. Ramos-Casals M, García-Hernández FJ, de Ramón E et al. BIOGEAS Study Group. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clin Exp Rheumatol 2010; 28(4):468-76.
5. Butterly SJ, Pillans P, Horn B, Miles R, Sturtevant J. Off label use of rituximab in a tertiary Queensland hospital. Int Intern Med J 2010; 40:443–452.
6. O'Connor K, Liddle C. Prospective data collection of off-label use of rituximab in Australian public hospitals. Intern Med J 2013; 43(8):863-70
7. Castillo-Trivino T, Braithwaite D, Bacchetti P, Waubant E. Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review. PLoS One 2013; 8(7):e66308.
8. Bar-Or A, Calabresi PA, Arnold D et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63(3):395-400.
9. Naismith RT, Piccio L, Lyons JA et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 2010; 74(23):1860-7.
10. Hauser SL, Waubant E, Arnold DL et al. HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358(7):676-88.
11. Alping P, Frisell T, Novakova L et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol 2016; 79(6):950-8.
12. de Flon P, Gunnarsson M, Laurell K et al. Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab. Neurology 2016; 87(2):141-7.
13. de Flon P, Laurell K, Söderström L, Gunnarsson M, Svenningsson A. Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS. Mult Scler 2017; 23(9):1249-1257.
14. Spelman T, Frisell T, Piehl F, Hillert J. Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Mult Scler. 2018; 24(8):1087-1095.
15. Hawker K, O'Connor P, Freedman MS et al. OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66(4):460-71.
16. Rommer PS, Patejdl R, Winkelmann A, Benecke R, Zettl UK. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs 2011; 25(7):607-13.
17. Salzer J, Svenningsson R, Alping P et al. Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy. Neurology 2016; 87(20):2074-2081.
18. Bittner S, Ruck T, Wiendl H, Grauer OM, Meuth SG. Targeting B cells in relapsing-remitting multiple sclerosis: from pathophysiology to optimal clinical management. Ther Adv Neurol Disord 2017; 10(1):51-66.
19. Gasperi C, Stüve O, Hemmer B. B cell-directed therapies in multiple sclerosis. Neurodegener Dis Manag 2016; 6(1):37-47.
20. McGonagle D, Tan AL, Madden J et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford) 2008; 47(4):552-3.
21. Lafyatis R, Kissin E, York M et al. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 2009; 60(2):578-83.
22. Bosello S, De Santis M, Lama G et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther 2010; 12(2):R54.
23. Smith V, Van Praet JT, Vandooren B et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 2010; 69 (1):193-7.
24. Daoussis D, Liossis SN, Tsamandas AC et al. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum 2010; 40(2):127-36.
25. Daoussis D, Liossis SN, Tsamandas AC et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford) 2010; 49(2):271-80.
26. Haroon M, McLaughlin P, Henry M, Harney S. Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids. Ther Adv Respir Dis 2011; 5(5):299-304.
27. Daoussis D, Antonopoulos I, Liossis SN, Yiannopoulos G, Andonopoulos AP. Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature. Semin Arthritis Rheum 2012; 41(6):822-9.
28. Daoussis D, Liossis SN, Tsamandas AC 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.
29. Smith V, Piette Y, van Praet JT et al. Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. J Rheumatol 2013; 40(1):52-7.
30. de Paula DR, Klem FB, Lorencetti PG, Muller C, Azevedo VF. Rituximab-induced regression of CREST-related calcinosis. Clin Rheumatol 2013; 32 (2):281-3.
31. Moazedi-Fuerst FC, Kielhauser SM, Brickmann K et al. Rituximab for systemic sclerosis: the arrest of pulmonary disease progression in five cases Results of a lower dosage and shorter interval regimen. Scand J Rheumatol 2014; 43 (3):257–8.
32. Jordan S, Distler JH, Maurer B et al. EUSTA Rituximab study group. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015; 74 (6):1188–94.
33. Bosello SL, De Luca G, Rucco M et al. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. Semin Arthritis Rheum 2015; 44(4):428–36.
34. Giuggioli D, Lumetti F, Colaci M, Fallahi P, Antonelli A, Ferri C. Rituximab in the treatment of patients with systemic sclerosis. Our experience and review of the literature. Autoimmunity Reviews 2015; 14 (11): 1072-8.
35. Kowal-Bielecka O, Fransen J, Avouac J et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76:1327–1339.
36. Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology (Oxford) 2017; 56(1):26-36.
37. Marie I. Therapy of polymyositis and dermatomyositis. Presse Med 2011; 40 (4 Pt 2):e257-70.
38. Oddis CV, Reed AM, Aggarwal R et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 2013; 65:314_24.
39. de Visser M. The efficacy of rituximab in refractory myositis: the jury is still out. Arthritis Rheum 2013; 65:303_6.
40. Verstappen GM, van Nimwegen JF, Vissink A, Kroese FGM, Bootsma H. The value of rituximab treatment in primary Sjögren's syndrome. Clin Immun 2017; 182:62-71.
41. Meiners PM, Vissink A, Kallenberg CG, Kroese FG, Bootsma H. Treatment of primary Sjögren's syndrome with anti-CD20 therapy (rituximab). A feasible approach or just a starting point? Expert Opin Biol Ther 2011; 11(10):1381-94.
42. Carubbi F, Alunno A, Cipriani P et al. Rituximab in primary Sjögren's syndrome: a ten-year journey. Lupus 2014; 23(13):1337-49.
43. Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjögren syndrome with rituximab: a randomized trial. Ann Intern Med 2014; 160(4):233-42.
44. Bowman SJ, Everett CC, O'Dwyer JL et al. Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren's Syndrome. Arthritis Rheumatol 2017; 69(7):1440-1450.
45. Carsons SE, Vivino FB, Parke A et al. Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain. Arthritis Care Res (Hoboken) 2017; 69(4):517-527.
46. Saeed M, Dabbagh O, Al-Muhaizae M, Dhalaan H, Chedrawi A. Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection. J Coll Physicians Surg Pak 2014; 24 Suppl 3:S216-8.
47. Rodríguez-Porcel F, Hornik A, Rosenblum J, Borys E, Biller J. Refractory Fulminant Acute Disseminated Encephalomyelitis (ADEM) in an Adult. Front Neurol 2014; 5:270.
48. American Cancer Society. Off-label drug use. Available at: http:// www.cancer.org/Treatment TreatmentsandSideEffects/TreatmentTypes/Chemotherapy/off-label-drug-use. Accessed 11 Nov 2012.
2. Danés I, Agustí A, Vallano A, et al. Available evidence and outcome of off-label use of rituximab in clinical practice. Eur J Clin Pharmacol 2013; 69(9):1689-99.
3. Van Allen EM, Miyake T, Gunn N, Behler CM, Kohlwes J. Off-label use of rituximab in a multipayer insurance system. J Oncol Pract 2011;7:76–79.
4. Ramos-Casals M, García-Hernández FJ, de Ramón E et al. BIOGEAS Study Group. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clin Exp Rheumatol 2010; 28(4):468-76.
5. Butterly SJ, Pillans P, Horn B, Miles R, Sturtevant J. Off label use of rituximab in a tertiary Queensland hospital. Int Intern Med J 2010; 40:443–452.
6. O'Connor K, Liddle C. Prospective data collection of off-label use of rituximab in Australian public hospitals. Intern Med J 2013; 43(8):863-70
7. Castillo-Trivino T, Braithwaite D, Bacchetti P, Waubant E. Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review. PLoS One 2013; 8(7):e66308.
8. Bar-Or A, Calabresi PA, Arnold D et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63(3):395-400.
9. Naismith RT, Piccio L, Lyons JA et al. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 2010; 74(23):1860-7.
10. Hauser SL, Waubant E, Arnold DL et al. HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358(7):676-88.
11. Alping P, Frisell T, Novakova L et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol 2016; 79(6):950-8.
12. de Flon P, Gunnarsson M, Laurell K et al. Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab. Neurology 2016; 87(2):141-7.
13. de Flon P, Laurell K, Söderström L, Gunnarsson M, Svenningsson A. Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS. Mult Scler 2017; 23(9):1249-1257.
14. Spelman T, Frisell T, Piehl F, Hillert J. Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Mult Scler. 2018; 24(8):1087-1095.
15. Hawker K, O'Connor P, Freedman MS et al. OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66(4):460-71.
16. Rommer PS, Patejdl R, Winkelmann A, Benecke R, Zettl UK. Rituximab for secondary progressive multiple sclerosis: a case series. CNS Drugs 2011; 25(7):607-13.
17. Salzer J, Svenningsson R, Alping P et al. Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy. Neurology 2016; 87(20):2074-2081.
18. Bittner S, Ruck T, Wiendl H, Grauer OM, Meuth SG. Targeting B cells in relapsing-remitting multiple sclerosis: from pathophysiology to optimal clinical management. Ther Adv Neurol Disord 2017; 10(1):51-66.
19. Gasperi C, Stüve O, Hemmer B. B cell-directed therapies in multiple sclerosis. Neurodegener Dis Manag 2016; 6(1):37-47.
20. McGonagle D, Tan AL, Madden J et al. Successful treatment of resistant scleroderma-associated interstitial lung disease with rituximab. Rheumatology (Oxford) 2008; 47(4):552-3.
21. Lafyatis R, Kissin E, York M et al. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 2009; 60(2):578-83.
22. Bosello S, De Santis M, Lama G et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther 2010; 12(2):R54.
23. Smith V, Van Praet JT, Vandooren B et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis 2010; 69 (1):193-7.
24. Daoussis D, Liossis SN, Tsamandas AC et al. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum 2010; 40(2):127-36.
25. Daoussis D, Liossis SN, Tsamandas AC et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford) 2010; 49(2):271-80.
26. Haroon M, McLaughlin P, Henry M, Harney S. Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids. Ther Adv Respir Dis 2011; 5(5):299-304.
27. Daoussis D, Antonopoulos I, Liossis SN, Yiannopoulos G, Andonopoulos AP. Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature. Semin Arthritis Rheum 2012; 41(6):822-9.
28. Daoussis D, Liossis SN, Tsamandas AC 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.
29. Smith V, Piette Y, van Praet JT et al. Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. J Rheumatol 2013; 40(1):52-7.
30. de Paula DR, Klem FB, Lorencetti PG, Muller C, Azevedo VF. Rituximab-induced regression of CREST-related calcinosis. Clin Rheumatol 2013; 32 (2):281-3.
31. Moazedi-Fuerst FC, Kielhauser SM, Brickmann K et al. Rituximab for systemic sclerosis: the arrest of pulmonary disease progression in five cases Results of a lower dosage and shorter interval regimen. Scand J Rheumatol 2014; 43 (3):257–8.
32. Jordan S, Distler JH, Maurer B et al. EUSTA Rituximab study group. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015; 74 (6):1188–94.
33. Bosello SL, De Luca G, Rucco M et al. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. Semin Arthritis Rheum 2015; 44(4):428–36.
34. Giuggioli D, Lumetti F, Colaci M, Fallahi P, Antonelli A, Ferri C. Rituximab in the treatment of patients with systemic sclerosis. Our experience and review of the literature. Autoimmunity Reviews 2015; 14 (11): 1072-8.
35. Kowal-Bielecka O, Fransen J, Avouac J et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis 2017; 76:1327–1339.
36. Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology (Oxford) 2017; 56(1):26-36.
37. Marie I. Therapy of polymyositis and dermatomyositis. Presse Med 2011; 40 (4 Pt 2):e257-70.
38. Oddis CV, Reed AM, Aggarwal R et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 2013; 65:314_24.
39. de Visser M. The efficacy of rituximab in refractory myositis: the jury is still out. Arthritis Rheum 2013; 65:303_6.
40. Verstappen GM, van Nimwegen JF, Vissink A, Kroese FGM, Bootsma H. The value of rituximab treatment in primary Sjögren's syndrome. Clin Immun 2017; 182:62-71.
41. Meiners PM, Vissink A, Kallenberg CG, Kroese FG, Bootsma H. Treatment of primary Sjögren's syndrome with anti-CD20 therapy (rituximab). A feasible approach or just a starting point? Expert Opin Biol Ther 2011; 11(10):1381-94.
42. Carubbi F, Alunno A, Cipriani P et al. Rituximab in primary Sjögren's syndrome: a ten-year journey. Lupus 2014; 23(13):1337-49.
43. Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjögren syndrome with rituximab: a randomized trial. Ann Intern Med 2014; 160(4):233-42.
44. Bowman SJ, Everett CC, O'Dwyer JL et al. Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren's Syndrome. Arthritis Rheumatol 2017; 69(7):1440-1450.
45. Carsons SE, Vivino FB, Parke A et al. Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain. Arthritis Care Res (Hoboken) 2017; 69(4):517-527.
46. Saeed M, Dabbagh O, Al-Muhaizae M, Dhalaan H, Chedrawi A. Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection. J Coll Physicians Surg Pak 2014; 24 Suppl 3:S216-8.
47. Rodríguez-Porcel F, Hornik A, Rosenblum J, Borys E, Biller J. Refractory Fulminant Acute Disseminated Encephalomyelitis (ADEM) in an Adult. Front Neurol 2014; 5:270.
48. American Cancer Society. Off-label drug use. Available at: http:// www.cancer.org/Treatment TreatmentsandSideEffects/TreatmentTypes/Chemotherapy/off-label-drug-use. Accessed 11 Nov 2012.
| Files | ||
| Issue | Vol 7, Vol 1-2 (Spring 2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v7i1-2.1617 | |
| Keywords | ||
| Rituximab Drug Utilization Evaluation Multiple Sclerosis | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Farasatinasab M, Aghabeigi S, Ramezaninejad S, Amouzegar A, Ghanbari B, Pakdaman N, Motamed MR, Almasi S, Rezaie N, Nasiripour S, Sabzghabaei F, Basi A. Rituximab Utilization Evaluation with Focused on Available Evidence for Off-Labeled Indications. J Pharm Care. 2019;7(1-2):14-20.
