Current and future treatment options for SSc

Dr Victoria Flower

Rheumatology Specialty Registrar

RNHRD, Bath

Systemic Sclerosis

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

Systemic Sclerosis

Raynaud’s Phenomenon

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

Raynaud’s phenomenon

• Cold, white/blue red

• Painful hands and reduced fine movement during attacks

Endothelium

• Aim to dilate the blood vessels to improve blood flow and warmth to fingers

Raynaud’s phenomenon

• Nifedipine*

• Iloprost

• Bosentan

• Sildenafil

• Reduce frequency and severity of attacks

• Heal ulcers

• Reduce new ulcers occurring

Raynaud’s Phenomenon

Nifedipine

• Tablet three times a day

• Blood pressure

• Dizziness

Iloprost

• Intravenous

• In hospital

• Nausea

• Diarrhoea

• Muscle cramp

• Headaches/jaw pain

• blood pressure

• Flushing

• Expensive

Bosentan

• Dizzy

• Flushing

• Liver tests

• May reduce OCP

• Rarely haemoptysis

Raynaud’s phenomenon

• Digital ulcers

• Infection

• Antibiotics as well as dilating treatments

Scleroderma

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

Limited cutaneous SSc

• If no lung disease then manage symptoms

• Treat Raynaud’s / ulcers/ infection

• Hand therapy

• Monitor

• Early sausage swelling of fingers may benefit from low dose steroids & antihistamines

Progressive Diffuse or lung disease

Maintenance

Induction Cyclophosphamide

Lung, heart, progressive skin

Methotrexate

Skin, arthritis, muscle

inflammation

Mycophenolate, Azathoprine

Predominantly lung disease

Cyclophosphamide

What is it?

• Also used for other conditions as well – lupus, vasculitis

• Intravenous injection (4-6 ‘cycles’)

• Takes up to 6 weeks to work

• Live vaccines ✗

• Annual Pneumovax ✓

Side effects:

• Nausea is common

• Haemorrhagic cystitis

• Monitor for white blood cells dropping and infection

• Fertility/contraception

Methotrexate

What is it?

• Used for many Rheumatological conditions

• Once a week

• Anti-folate

• Weekly folic acid supplement

• Monthly blood test monitoring

• Takes up to 12 weeks to work

• Live vaccines ✗

• Annual Pneumovax ✓

Side effects:

• Mouth ulcers

• Nausea

• Hair thinning (usually minor)

• Blood count

• Liver function tests

• Rarely lung inflammation

Calcinosis

• Treat infection

• Unfortunately no targeted treatments for calcium deposits

• Sometimes surgery but avoid if possible

Arthritis – joint pain and swelling

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

Hydroxychloroquine, Methotrexate and Mycophenolate mofetil

Hydroxychloroquine

• “Plaquenil” • Takes up to 12 weeks to work • Usually well tolerated with few side effects

Side effects: • Skin rash • Can exacerbate psoriasis • Indigestion • Headaches • Rarely visual problems 1 in 2000

Upper Gastrointestinal problems Oesophageal dysmotility

Difficulty swallowing

Painful swallow

Indigestion and acid reflux

GORD

PPIs to reduce acid

Prokinetics

Thrush

Antibiotics - Fluconazole

Delayed emptying of stomach Bloating, Early satiety Wind Prokinetics – domperidone, metoclopramide

Lower Gastrointestinal problems Reduced movement (peristalsis) of small bowel

Bloating, wind and constipation Laxatives

Diarrhoea Loperamide

Bacterial overgrowth Rotated antibiotics

Reduced absorption of nutrients Nutritional advice & supplements Rarely TPN

Systemic Sclerosis lung disease

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

Lungs Symptoms: Short of breath Cough Chest pain Fatigue Ankle swelling

Fibrosis: Cyclophosphamide Mycophenolate mofetil Azathioprine Steroids Aim to improves symptoms, breathing tests and QoL

Pulmonary hypertension: Warfarin, water tablets Bosentan Sildenafil Iloprost (as an inhaler) Epoprostinol (as a continuous infusion) Improves exercise tolerance, day to day symptoms and function, improves heart pressure

Kidney – Scleroderma renal crisis High Blood pressure Frothy urine Persistent headache Blurred vision Ankle swelling Short of breath

ACEI - lower BP Improves survival and reduces need for long term dialysis. Dialysis

Steroids in SSc: Monitor BP, urine dipstick and kidney blood test Avoid high dose steroids if at risk of SRC

The future for Systemic Sclerosis

Autoimmune

• Immune system produces cytokines

• Inflammation

Overproduction of Collagen

•Scar tissue forms, thickening of soft tissues

Blood vessel damage

•Reduces blood flow to tissues causing damage

•Encourages calcium deposits

EULAR SSc Trials and Research Group - EUSTAR

Canadian SSc research group SSc Research Foundation

Rituximab, Abatacept, Tocilizumab Autologous Stem cell transplant

References

(1)Thompson AE, Shea B, Welch V, Fenlon D, Pope JE. Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum 2001;44:1841–7. (2) Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, et al. Iloprost and cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev 1998;(2):CD000953. doi: 10.1002/14651858.CD000953. (3) Rademaker M, Cooke ED, Almond NE, Beacham JA, Smith RE, Mant TG, et al. Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud’s phenomenon in patients with systemic sclerosis: a double blind randomised study. BMJ 1989;298:561–4. (4) Scorza R, Caronni M, Mascagni B, Berruti V, Bazzi S, Micallef E, et al. Effects of long- term cyclic iloprost therapy in systemic sclerosis with Raynaud’s phenomenon. A randomized, controlled study. Clin Exp Rheumatol 2001;19:503–8. (5) Wigley FM, Seibold JR, Wise RA, McCloskey DA, Dole WP. Intravenous iloprost treatment of Raynaud’s phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 1992;19:1407–14. (6) Wigley FM, Wise RA, Seibold JR, McCloskey DA, Kujala G, Medsger TA Jr, et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med 1994;120:199–206. (7) Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized controlled trial. Ann Intern Med 2000;132:425–34. (8) EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR) O Kowal-Bielecka,1 R Landew ́e,2 J Avouac,3 S Chwiesko,1 I Miniati,4 L Czirjak,5 P Clements,6 C Denton,7 D Farge,8 K Fligelstone,9 I F ̈oldvari,10 D E Furst,6 U M ̈uller- Ladner,11 J Seibold,12 R M Silver,13 K Takehara,14 B Garay Toth,15 A Tyndall,16 G Valentini,17 F van den Hoogen,18 F Wigley,19 F Zulian,20 Marco Matucci-Cerinic,4 and the EUSTAR co-authors