Lupus (2014) 23, 428–430 http://lup.sagepub.com
CASE REPORT
Successful application of belimumab in two patients with systemic lupus erythematosus experiencing a flare during tocilizumab treatment M Ju¨ptner, R Zeuner, S Schreiber, M Laudes and JO Schro¨der Universita¨tsklinikum Schleswig-Holstein, Campus Kiel, Klinik fu¨r Innere Medizin I, Kiel, Germany
This case report describes two female lupus patients who both received biological treatment with tocilizumab and with belimumab. The disease course was remarkably similar in both cases. Tocilizumab resulted in a transient improvement in pleurisy and arthritis but was then followed by a clinical flare accompanied by an increase in autoantibodies and a drop in complement levels. Alike, both patients experienced a rapid and sustained improvement after institution of belimumab. The clinical benefit obtained is currently stable under ongoing belimumab therapy. Lupus (2014) 23, 428–430. Key words: Systemic lupus erythematosus; tocilizumab; belimumab
Introduction
Case presentation
The number of drugs approved for systemic lupus erythematosus is still very limited. Recently, several biologic agents have been evaluated in controlled trials and case series. So far, only the monoclonal BAFF-antibody belimumab has been licensed because of clinical benefit demonstrated in controlled trials. Compounds such as rituximab and abatacept failed to achieve their primary endpoint in trials in non-renal lupus as well as in lupus nephritis.1,2 TNF-inhibitors, despite delivery of shortterm benefit, turned out to be rather detrimental in the long term.3 Other approaches, for example, targeting of interferon-a or interleukin-6, currently are under evaluation. Therefore, information on the relative value of biologics in systemic lupus is scarcely available. Here, we report on two patients, who consecutively received tocilizumab and belimumab with remarkably opposed results.
Patient one is a 46-year-old female with a 23-year history of systemic lupus. Her manifestations included thrombocytopaenia, anaemia, arthritis and severe pleuritis. Hydroxychloroquine, azathioprine, mycophenolate, methotrexate, nine infusions of intravenous cyclophosphamide and two infusions of rituximab had not been tolerated or had failed to control the disease. On the basis of preliminary data,4 we decided to introduce off-label tocilizumab (8 mg/kg body weight per month) in addition to 10 mg of prednisolone per day. After three cycles of tocilizumab and a short-term and partial improvement in pleuritis and anaemia, the patient presented with a severe flare including a butterfly rash (Figure 1), fever, weight loss, joint swelling and a drop in her platelet count. In parallel, complements C4 and C3 had distinctly declined. The SLEDAI had increased from a score of 10 to 13. After a transient increase in the prednisolone dose, we decided to introduce the meanwhile licensed belimumab (10 mg/kg body weight per month). Within six months, all manifestations except minor pleuritic pain resolved. Complement levels normalized, and ds-DNA antibodies continuously declined to a value slightly above the reference range. The resulting SLEDAI decreased to a score of 4 (Table 1).
Correspondence to: Johann Oltmann Schro¨der, Universita¨tsklinikum Schleswig-Holstein, Campus Kiel, Klinik fu¨r Innere Medizin I – Sektion Rheumatologie, Arnold-Heller-Straße 3, Haus 5, D-24105 Kiel, Germany. Email: [email protected] Received 8 November 2013; accepted 23 December 2013 ! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UNIV OF MICHIGAN on February 19, 2015
10.1177/0961203314520844
Successful application of belimumab in two patients with SLE M Ju¨ptner et al.
429
Figure 1 (a) Patient 1: seven days after third infusion of tocilizumab: distinct butterfly rash of the right cheek; the nasolabial line is not afflicted. (b) Patient 2: paronychial nailfold infarcts of digit 5 right hand and digit 4 left hand after 15 infusions of tocilizumab.
Table 1 Serological markers of two patients: changes under treatment with tocilizumab and belimumab Tocilizumab Patient 1 ANA ds-DNA C3 C4 CRP Platelets Haemoglobin Prednisolone SLEDAI Patient 2
(titre) (U/l) (g/l) (g/l) (mg/l) (count/nl) (g/dl) (mg/d)
ANA ds-DNA C3 C4 CRP Platelets Haemoglobin Prednisolone SLEDAI
(titre) (U/l) (g/l) (g/l) (mg/l) (count/nl) (g/dl) (mg/d)
Belimumab
1/2012
3/2012
4/2012
7/2013
1:10,240 533 0.95 0.07 30.6 229 10.2 10 10 Tocilizumab 1/2011 1:20,480 28 0.78
CASE REPORT
Successful application of belimumab in two patients with systemic lupus erythematosus experiencing a flare during tocilizumab treatment M Ju¨ptner, R Zeuner, S Schreiber, M Laudes and JO Schro¨der Universita¨tsklinikum Schleswig-Holstein, Campus Kiel, Klinik fu¨r Innere Medizin I, Kiel, Germany
This case report describes two female lupus patients who both received biological treatment with tocilizumab and with belimumab. The disease course was remarkably similar in both cases. Tocilizumab resulted in a transient improvement in pleurisy and arthritis but was then followed by a clinical flare accompanied by an increase in autoantibodies and a drop in complement levels. Alike, both patients experienced a rapid and sustained improvement after institution of belimumab. The clinical benefit obtained is currently stable under ongoing belimumab therapy. Lupus (2014) 23, 428–430. Key words: Systemic lupus erythematosus; tocilizumab; belimumab
Introduction
Case presentation
The number of drugs approved for systemic lupus erythematosus is still very limited. Recently, several biologic agents have been evaluated in controlled trials and case series. So far, only the monoclonal BAFF-antibody belimumab has been licensed because of clinical benefit demonstrated in controlled trials. Compounds such as rituximab and abatacept failed to achieve their primary endpoint in trials in non-renal lupus as well as in lupus nephritis.1,2 TNF-inhibitors, despite delivery of shortterm benefit, turned out to be rather detrimental in the long term.3 Other approaches, for example, targeting of interferon-a or interleukin-6, currently are under evaluation. Therefore, information on the relative value of biologics in systemic lupus is scarcely available. Here, we report on two patients, who consecutively received tocilizumab and belimumab with remarkably opposed results.
Patient one is a 46-year-old female with a 23-year history of systemic lupus. Her manifestations included thrombocytopaenia, anaemia, arthritis and severe pleuritis. Hydroxychloroquine, azathioprine, mycophenolate, methotrexate, nine infusions of intravenous cyclophosphamide and two infusions of rituximab had not been tolerated or had failed to control the disease. On the basis of preliminary data,4 we decided to introduce off-label tocilizumab (8 mg/kg body weight per month) in addition to 10 mg of prednisolone per day. After three cycles of tocilizumab and a short-term and partial improvement in pleuritis and anaemia, the patient presented with a severe flare including a butterfly rash (Figure 1), fever, weight loss, joint swelling and a drop in her platelet count. In parallel, complements C4 and C3 had distinctly declined. The SLEDAI had increased from a score of 10 to 13. After a transient increase in the prednisolone dose, we decided to introduce the meanwhile licensed belimumab (10 mg/kg body weight per month). Within six months, all manifestations except minor pleuritic pain resolved. Complement levels normalized, and ds-DNA antibodies continuously declined to a value slightly above the reference range. The resulting SLEDAI decreased to a score of 4 (Table 1).
Correspondence to: Johann Oltmann Schro¨der, Universita¨tsklinikum Schleswig-Holstein, Campus Kiel, Klinik fu¨r Innere Medizin I – Sektion Rheumatologie, Arnold-Heller-Straße 3, Haus 5, D-24105 Kiel, Germany. Email: [email protected] Received 8 November 2013; accepted 23 December 2013 ! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UNIV OF MICHIGAN on February 19, 2015
10.1177/0961203314520844
Successful application of belimumab in two patients with SLE M Ju¨ptner et al.
429
Figure 1 (a) Patient 1: seven days after third infusion of tocilizumab: distinct butterfly rash of the right cheek; the nasolabial line is not afflicted. (b) Patient 2: paronychial nailfold infarcts of digit 5 right hand and digit 4 left hand after 15 infusions of tocilizumab.
Table 1 Serological markers of two patients: changes under treatment with tocilizumab and belimumab Tocilizumab Patient 1 ANA ds-DNA C3 C4 CRP Platelets Haemoglobin Prednisolone SLEDAI Patient 2
(titre) (U/l) (g/l) (g/l) (mg/l) (count/nl) (g/dl) (mg/d)
ANA ds-DNA C3 C4 CRP Platelets Haemoglobin Prednisolone SLEDAI
(titre) (U/l) (g/l) (g/l) (mg/l) (count/nl) (g/dl) (mg/d)
Belimumab
1/2012
3/2012
4/2012
7/2013
1:10,240 533 0.95 0.07 30.6 229 10.2 10 10 Tocilizumab 1/2011 1:20,480 28 0.78
