Friday, 22 Jun 2018

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Lupus Management After Failure of First-Line Treatment

There are no detailed recommendations agreed upon by SLE experts on what treatment to use after first and second (and often third) line treatment has failed.

In an attempt to fill in the knowledge gap for SLE treatment, several SLE experts were polled. Using cases that were organ-based, experts were asked to write what they would do first, then second, then third, etc., assuming all treatment was available, tolerated and enough time was given to determine the treatment was not successful.

This is in press in Arthritis Care & Research ("Treatment algorithms in systemic lupus erythematosus," by Muangchan C, et al). What was striking is that some organs had very good agreement despite lack of RCT data (myocarditis, ILD, vasculitis) whereas other treatment strategies had some RCT data but poor agreement (APS, ITP). Also rituximab treatment that is not approved in SLE (with negative RCT data) was frequently in the treatment algorithm. The take home message is that there is a need to continue developing treatment strategies in SLE that are both evidence and eminence based with the knowledge that the options used and doses of steroids will vary with the organ involved and the severity/activity of the patient. These are artificial scenarios in that many patients may have more than one organ involved with disease activity and may be partial responders to treatment or have side effects or comorbidities so treatment cannot be increased, but the consensus in various organs can help guide treatment particularly for those who are not expert in SLE treatment.

Treatment algorithm for organ system involvements by systemic lupus erythematosus

Organ involvement

Treatment options

Ancillary

therapy

% Agreement

(median)

1st-line or Induction

2nd-line or Failure of induction

3rd-line

Maintenance

1. Constitutional symptoms

GC, HCQ, IMM or combinations

MMF

Switching to

RTX or BLM

N/A

N/A

60

2. Widespread DLE

HCQ ± GC

Adding AZA or switching antimalarial

Switching AZA to

MMF

or MTX

N/A

Sun screening + Topical steroids or Topical tacrolimus

70

3. Uncomplicated digital/ cutaneous vasculitis

GC ± HCQ ± MTX

AZA or MMF

Switching to

IV CYC

N/A

N/A

80

4. Gangrenous digital/ cutaneous vasculitis

GC + IV CYC

Adding RTX

or PLAX

N/A

AZA or MMF

PGA

90

5. Non-erosive, non-deforming polyarthritis

HCQ ± GC

Adding MTX

Adding RTX

N/A

NSAIDs

80

6. Lupus pericarditis

GC ± HCQ

Adding MMF

or AZA or MTX

Adding BLM

or RTX

N/A

Pericardiocentesis ± window

75

7. Lupus myocarditis

GC + IV CYC

± HCQ

Adding RTX

or BLM or IVIG

N/A

MMF

N/A

90

8. Lupus ILD

GC + MMF

or IV CYC

Adding RTX

or IVIG

N/A

AZA or MMF

N/A

90

9. Lupus PAH

GC + IV CYC

or MMF + ERA

Adding RTX, and PDE5i

Adding PGA

MMF

N/A

80

10. Lupus thrombocytopenia

GC ± HCQ

Adding AZA or MMF

Adding RTX

or IV CYC or IVIG

N/A

Splenectomy

50

11. Lupus- APS- venous thrombosis

Anticoagulation (Warfarin or Low molecular weight heparin)

± HCQ

Direct thrombin inhibitor

N/A

N/A

N/A

60

12. Lupus- APS- arterial thrombosis

Anticoagulation

(Warfarin or Low molecular weight heparin)

± HCQ

Adding ASA

or Dipyridamole

or PAI

N/A

N/A

N/A

70

13. Lupus mononeuritis multiplex

GC + IV CYC

Adding RTX

or IVIG or PLAX

N/A

AZA or MMF

N/A

75

14. CNS lupus

GC + IV CYC

Adding RTX

or IVIG or PLAX

N/A

AZA or MMF

N/A

60

15. LN type III / IV

GC + MMF

IV CYC

Adding RTX

MMF

HCQ, ACEI

70

16. LN type V

GC + MMF

Switching to AZA or IV CYC or RTX

N/A

MMF

HCQ, ACEI

80


Abbreviation: systemic glucocorticoids: GC; hydroxychloroquine: HCQ; methotrexate: MTX; immunomodulators: IMM i.e. HCQ or low dose weekly MTX; azathioprine: AZA; mycophenolate mofetil: MMF; cyclophosphamide: CYC; rituximab: RTX; belimumab: BLM; plasmapheresis: PLAX; intravenous immunoglobulins: IVIG; endothelin receptor antagonist: ERA; phosphodiesterase-5 inhibitor: PDE5i; prostanoids / prostaglandins analogues: PGA; platelets aggregation inhibitor: PAI; angiotensin converting enzyme inhibitor: ACEI; NSAIDs: nonsteroidal anti-inflammatory drugs; not available: N/A

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Dr. Pope is a Professor of Medicine at Western University, London, Ontario, Canada. She is a rheumatologist and epidemiologist and is Division Head in Rheumatology at St. Joseph’s Hospital, London, Ontario. She has a major interest in scleroderma including membership in the Canadian Scleroderma Research Group (CSRG), Scleroderma Clinical Trials Consortium (SCTC) and co-leading the new ACR/EULAR guidelines for SSc and has published over 250 peer reviewed articles. She was named the Canadian Rheumatology Association Distinguished Investigator in 2013 and Rheumatologist of the Year from the Ontario Rheumatology Association. She supervises students at all levels and runs two nationwide studentships for medical students to be exposed to clinical rheumatology or research in rheumatology.