What are the treatments in Wegener’s Granulomatosis (GPA)?

The main aim of treatment is to rapidly get inflammation under control in order to limit organ damage. Treatment choices usually depend on whether there is limited or more widespread disease and how severe the condition is. Patients with serious organ involvement will need treatment with medicines such as steroids and drugs to suppress the immune system. Over the last ten years there has been a wealth of information from international clinical trials especially in Europe from the European Vasculitis Study Group. These trials have led to more defined treatment protocols, which have improved the outcomes of patients with fewer side-effects. For most seriously ill patients, a combination of drugs such as steroids and cyclophosphamide remains the best way of getting an early response – in many patients this can be life-saving. This is then followed by a more gentle immune-suppressing approach using different drugs, for example azathioprine, to keep the patient in remission over the longer term. More recently, biologic agents such as rituximab, which targets the antibody producing cells of the immune system, have revolutionised treatment, leading to less use of cyclophosphamide which can be toxic.

Medications

Steroids

One of the first medicines used in GPA are corticosteroids (steroids) which rapidly reduce inflammation throughout the body. Prednisone and prednisolone are the most commonly used oral steroids in the UK. Doses are variable depending how severe the Rheumatologist feels the disease is. Steroids are usually well tolerated although have long term side effects if used at high doses for over six months. These may include weight gain, mood swings, osteoporosis, high blood pressure and diabetes. Therefore you will find that your doctor will want to reduce your dose as quickly as possible.

To counteract some of these steroid side effects, your doctor may also prescribe Calcium supplements and a bisphosphonate, which prevents bone breakdown and is used in the treatment and prevention of osteoporosis. An antacid medication, known as a proton-pump inhibitor may also be used to prevent excessive heartburn.

Steroid-Sparing Agents

Steroid-sparing medications are frequently used in combination with steroids to limit the dose and side-effects of steroids. They tend to work more slowly at modifying the inflammation but do not have the steroid side effects and therefore may be a better long term option. The use of these drugs frequently allows the dose of prednisolone to be reduced to very small doses that keep the condition under control and minimize long term side-effects. In a small minority of patients, steroids can even be withdrawn altogether. Frequently used medicines include Cyclophosphamide, Methotrexate, Azathioprine and Mycophenolate Mofetil. They are often also referred to as immunosuppressants. Many of these drugs were first used in the treatment of cancer, and cyclophosphamide in particular has a reputation as a ‘chemotherapy’ drug. Whilst side effects are numerous and potentially serious, physicians have learned to use much smaller doses of these agents than those used in cancer with the result that these drugs are extremely effective but the side-efects are tolerable. These drugs do require regular monitoring of the blood, as the full blood count and liver function can be affected (see links for the ARC drug information leaflets).

Using these combinations of drugs, up to 90% of patients may go into a remission from their disease. However, disease ‘flares’ occur frequently in GPA (between 60 and 80% of patients) and so treatment may last for many years and most patients will need very long term monitoring of their condition.

As GPA is a disease of the immunity and most of these medications affect the immune system, your ability to fight certain infections can be reduced. For this reason, doctors may prescribe an antibiotic, Co-Trimoxazole (Septrin), to reduce the risk of chest and sinus infections.

Biologic drugs

Biologic drugs have significantly improved the clinical prognosis of severe GPA (click here for the abstract of our published paper on the subject). Rituximab is an intravenous medication used in treating the auto-immune disorders Rheumatoid Arthritis and Lupus (Systemic Lupus Erythematosus or SLE) and cancers such as lymphoma. Rituximab was found to be as effective as cyclophosphamide in patients with severe GPA and clinical trials led to approval by the US FDA and the European agencies for use in GPA, especially in patients who experience disease relapses. It works by reducing the number of B-cells (a type of white blood cell) that drive the inflammatory process. However, Rituximab can significantly hamper the immune system, so infections are a risk.

Surgical options

Surgical treatments are reserved for limited complications of GPA. They are used as an adjunct to the above medical therapies. Surgical biopsies are also used to aid diagnosis of GPA.

Occasionally, nasal and tracheal (windpipe) disease can lead to tightening, known as fibrosis, and narrowing of the airways. In severe cases, surgical dilatation or corticosteroid injections can be of benefit. These procedures are usually performed by Ear, Nose and Throat (ENT) surgeons. These doctors may also be involved in the care of a non-resolving sinus or nasal infection that has failed to respond fully to antibiotics. In these cases, a small procedure to drain pockets of infection may be necessary.

Please click here for the A4 Wegener’s Trust leaflet