Targeting vasculitis

The patients' experience

Note This section contains testimonies and photos from individual patients who took Campath-1H in clinical trials. These were put together by Millie Brierley for an exhibition 'Care at the Leading Edge', 1999, which was designed to educate both the public and medical practitioners about vasculitis. The stories that appear in this section reveal as much about how individuals cope with a chronic disease as about the early expriences of patients who received Campath-1H. Unless specified, all the names of patients and their relatives are pseudonyms. The stories told are unique and should not be read as definitive statements about the benefits and side effects of alemtuzumab. Outcomes are influenced by many factors and may vary from patient to patient. The drug should only be considered as a treatment option after extensive consultations between a patient and their own medical practitioners.

This shows Martin Lockwood, a consultant at Addenbrooke's Hospital in Cambridge who specialised in the treatment of vasculitis disease. Credit: Millie Brierley.

Early on in his development of alemtuzumab, Waldmann wondered whether the drug might be beneficial for a number of autoimmune diseases, due to the fact that it depleted T-cells which were often the cause of such conditions. To this end, Waldmann encouraged collaborations with clinicians working on autoimmune diseases so that he could extend its testing beyond his original remit for improving BMTS. Such testing was undertaken with supplies of the drug from the TAC.

In 1987, Waldmann was approached by Martin Lockwood, a consultant physician at Addenbrooke's Hospital, who had just moved to Cambridge after working in a renal unit at Hammersmith Hospital as a senior clinical research fellow. Lockwood was interested in testing Campath-1H on patients suffering from vasculitis, a serious and often fatal disease where the immune system attacks blood vessels and causes inflammation of the arteries, veins and capillaries. Patients can experience symptoms such as fever, swelling, malaise, and fatigue as well as the loss of the function of a particular tissue or organ. The disease is associated with autoimmune disorders such as lupus, Behcet's disease, Wegener's granulomatosis and polyarteritis.

Lockwood had first come across vasculitis while working as a senior registrar in the renal unit at Hammersmith Hospital during the 1970s. At the time the rental unit was a hotbed of research into immune mechanisms in renal disease. During his time there, Lockwood had treated patients suffering from Goodpasture's syndrome. This is a rare autoimmune disorder where a patient's own antibodies attack their lungs and kidneys. It can result in the permanent and often fatal injury of the lungs and kidneys. Looking to improve the care of such patients, Lockwood, encouraged by his mentor Keith Peters, pioneered a new procedure known as plasmapheresis. Similar to kidney dialysis, this technique proved remarkably effective in reducing renal failure. It involved taking plasma from a patient, spinning it to remove the harmful antibodies that caused the syndrome, and then infusing the plasma back into the patient. Lockwood had also undertaken laboratory research to investigate the mechanisms underlying the regulation of auto-immune responses and developed serological diagnostics to identify patients with auto antibodies associated with auto-immune diseases like vasculitis.

On arriving in Cambridge, Lockwood continued developing his work on auto-immunity. Understanding Campath-1H to be a monoclonal antibody directed against lymphocytes, which were known to underline the auto-immune process, he wondered whether the drug might offer a treatment for vasculitis. One of the attractions of Campath-1H was that it offered a more effective and specific control of the auto-immune disease without the side effects inherent in the then available broad spectrum of immunosuppressive agents.

This photograph shows Lockwood with his colleagues at Addenbrooke's Hospital. Credit: Millie Brierley.

In November 1988, Lockwood together with Waldmann and his team launched a pilot test of Campath-1H in a man with systemic vasculitis. The patient had first started experiencing symptoms of his disease when aged 40 and had suffered for 25 years. He had received various conventional drugs over time, but by 1987 he was greatly deteriorating. His condition had improved with five plasma exchanges. Thereafter he continued to receive monthly plasma exchanges, but he tolerated them poorly. By the time that Lockwood and Waldmann decided to give him Campath-1H, he was experiencing high fluctuating fevers, anorexia, weight loss, arthralgia and a bright red rash.

The test involved administering Campath-1H, to deplete the man's lymphocytes, followed by a CD4 monoclonal antibody so as stimulate his immune tolerance to whatever antigens he was reacting to. Within 48 hours of receiving his first dose of Campath-1H, given over eight days, the man's rash had dramatically improved and his fever abated. His remission only lasted ten days, but the therapy caused no serious side effects. This was a major step forward before up to now he had responded to conventional therapy only partially. He experienced to more short-lived remissions with two further courses of Campath-1H and remained well for 42 months after completing treatment. Click here to see photographs of the patient before and after his treatment with Campath-1H.

One of the most disturbing features of vasculitis was that it could strike people at a very young age. Indeed, many of the patients Lockwood saw were adolescents or young adults whose lives had been blighted by the disease. One such case was Nicola (real name). Forced to leave school as a result of autoimmune vasculitis, which she had first developed when aged thirteen, together with a crippling form of arthritis, Nicola had been referred to three different hospitals in an effort to diagnose and treat her disease. Most of her young life had been spent in hospital receiving every possible treatment doctors could give her to try and contain what was she describes as 'a virulent, damaging and progressive disease'. Her suffering was intense. As she recalled, 'my joints were extremely stiff, and if I attempted to move I was punished with excruciating pain.' Her immune and vascular systems had also been seriously impaired.

By December 1990, when Lockwood took over her care, Nicola was twenty years old. On her arrival Lockwood tried various standard and experimental therapies, but to no avail. Within a short space of time her illness had become so severe that all her internal organs were shutting down and her parents were told that she would not survive to Christmas. With no other alternatives, Lockwood offered to treat her with Campath-1G. Her parents realised this was terribly risky, but given she had little chance of survival, they agreed to the treatment. Within a few hours of receiving the drug, Nicola's inflammatory markers dropped dramatically and continued to do so. Click here for graphs documenting Campath-1H's impact on Nicola's inflammatory markers.

This is a photograph of Nicola. Credit: Millie Brierley.

Within days of receiving her first infusion, Nicola's health had improved so significantly she was able to stop the intravenous large doses of opiates she had been receiving to control her pain. Some time later, Nicola was able to return to normal activities, something she had been unable to do for years. Click here to see how Nicola reacted to going home after being discharged from hospital.

After her initial treatment in 1990, Nicola was given several more treatments with Campath-1H. Each time this resulted in a remission of her disease, but after three courses of the drug she developed an immune response to the antibody. Further infusions of the drug were successful after undergoing plasmapheresis to remove the harmful antibodies in her blood that were responsible for her negative immune reactions. Writing of her experiences with Campath-1H in 2003, she stated, 'After repeated treatments, my disease has changed and I have been able to undergo various operations, including replacement hips and knees. I am now able to walk a little WITHOUT aids, and I am eternally grateful!' Commenting on her complications with Campath-1H, she wrote, 'I remain forever hopeful that something like it will come up which will give me the same feeling of well-being and freedom that Campath once did.' Today, Nicola continues to live her life to full as much as possible. Click here for Nicola's follow-up story.

By 1993, Lockwood and Waldmann's team had treated four patients with severe systemic vasculitis who were unresponsive to conventional immunosuppressive drugs. Of these, three out of the four had experienced a substantial and sustained benefit from Campath and appeared to require no further treatment with the drug. Click here to see a summary of the data collected from the patients.

News of Lockwood's testing of Campath-1H in patients with vasculitis soon spread beyond the confines of Cambridge. In December 1993, Lockwood received a phone call from a paediatrician based in Sydney, Australia, to see whether the drug could possibly help his wife, Margaret (real name). She was desperately ill with polyarteritis nodosa microscopica, a life-threatening condition that is caused by vasculitis damaging the walls of the body's small and medium-sized arteries.

Margaret had initially begun to feel unwell shortly after the birth of her second child, in October 1992. Over the course of the next few months her health radpidly deteriorated, preventing her from taking care of both her new-born and 6 year old daughter. Diagnosed in July 1993, Margaret was prescribed various medications, including high doses of steroids, and a course of plasmapheresis, but all to no avail.

On witnessing Margaret's rapid decline, her husband began scouring Medline in a desperate attempt to find something to help her. Learning of Lockwood's work with Campath-1H, he swiftly arranged for Margaret to fly to England in January 1994 to receive the drug. Within weeks of her treatment, Margaret had sufficiently improved to be discharged to fly back to Sydney. By December 1994, she had recovered enough to relinquish her steroid medication and her body was beginning to return to normal. Thereafter she returned back to work full-time. Today, Margaret remains well and continues in remission apart from needing steroid eye drops for ongoing iritis after shingles. Grateful to Lockwood and the benefits of Campath-1H she describes herself as 'a miracle of modern medicine'. Click here for a detailed description of Margaret's experience.

By the mid-1990s, Lockwood was treating a number of patients with Campath-1H. One of his patients was Ellen who had spent many years since the age of 7 in and out of hospital with various symptoms. These ranged from having an unusually low white blood cell count, sores on her legs, exhaustion, pain in her ear and in her joints, vagina boils, pounding headaches, and drinking vast quantities of fluid. Yet, no doctor could diagnose what was wrong with her. Finally, in December 1998, a consultant at Northampton Hospital, on observing her fingertips were turning black, diagnosed her with Behcet's disease and referred her on to Lockwood's clinic.

This is a photograph of Ellen with her sister Vivian sitting on her left. Ellen received Campath-1H for Bechet's disease. Credit: Millie Brierley.

Behcet's disease is a lifelong, rare chronic inflammatory disorder that comes and goes. Its cause is unknown. Symptoms include recurrent ulcers in the mouth and on the genitals as well as eye inflammation. It can also cause various types of skin lesions, arthritis, bowel inflammation, meningitis and muscle paralysis in the cranial nerves controlling eye movement and facial expression. The disease can affect all organs and the central nervous system, causing memory loss and impaired speech, balance and movement. It can also lead to blindness, strokes, swelling of the spinal cord and intestinal complications.

After receiving Campath-1H, Ellen's health greatly improved, allowing her to start leading a normal life for the first time. In 2005, she needed a subsequent course of treatment, which, as she put it, had similarly 'outstanding benefits'. While still troubled by Behcet's disease, Campath-1H helped minimise her symptoms. In 2003, Ellen gave birth to her first child and three years later to a second. This was totally against all the odds, because, when first diagnosed with Behcet's disease she had been told treatment would impair her fertility. Ellen continues to lead an active life to this day. Click here for Ellen's story and here for Vivian, her sister's, story.

Another patient treated by Lockwood was Myrna (real name), a 60 year old registered nurse from Canada. Myrna had suffered various debilitating symptoms since she was 8 years old, including mouth ulcers, painful joints and stomach and bowel problems. It was only in 1991, when she was 53, however, that she was diagnosed with Behcet's disease. Over the next few years, she faced one health crisis after another, resulting in her losing her job, her self-esteem and the ability to pursue many of her favourite leisure pass times.

In her search for a cure, Myrna discovered other sufferers with Behcet's disease, fewer than 100 in Canada. Realising how little was known about the syndrome and that even doctors, as she put it, 'were flying by the seat of their pants', she set up a website for Behcet sufferers. As a result of this, she was contacted by a British woman in 1993. The woman had received Campath-1H the previous year and within 9 months of treatment had been able to move from Britain to Poland to head up a new branch office for her company. Learning how effective Campath-1H had been for this woman, Myrna campaigned for the British Columbian government to help pay for her to receive treatment in Britain. Her request for assistance, however, was turned down on the grounds that Campath-1H was still an experimental drug and not recognised in Canada. She eventually secured 5,000 Canadian dollars from friends and concerned residents to pay for her travel and subsistence costs to go to Cambridge for treatment.

This shows Myrna being treated at Lockwood's clinic in January 1999 for Behcet's disease. Credit: Millie Brierley.

A month after completing her treatment, Myrna wrote, 'I have felt pain free and really good ever since the Campath … I find that my body temperature has dropped. I feel extremely cool to touch externally and internally COOL ...... My friends and neighbours tell me I'm looking ten years younger, but I find I tire out quite early in the day and go to bed along with the birds!' Over the following months, she continued to gain her strength and 6 months after treatment she wrote, 'feel like a million bucks'. She would continue to live a full life offering help to other Behcet's disease patients until 2007 when she passed away due to a super bug she caught in hospital when treated for injuries from a fall. Click here for more about Myrna's experiences.

This shows Eleanor back home with her family once she had completed her treatment with Campath. Credit: Millie Brierley.

Among the patients that Lockwood cared for were those who had Wegener's Granulomatosis. This is a rare disorder involving inflammation of the blood vessels which reduces blood flow. The condition mainly affects blood vessels in the nose, sinuses, ears, lungs and kidneys, although other areas can also be involved. Click here to see the impact of Campath-1H on a patient with Wegener's granulomatosis.

One of the patients who had Wegener's Granulomatosis that Lockwood treated was Eleanor. She had first started getting symptoms of the disease when fifteen years old. Aged 34, when she arrived in Lockwood's clinic in 1990, Eleanor was experiencing acute problems in her nose and the back of her tongue. For some years she had managed to cope with these symptoms with the help of treatment from the Royal National Throat and Ear Hospital in London. Subsequently, however, she began to develop complications and was referred to Cambridge when her father, who was a doctor, read of Lockwood's work with Campath-1H in a medical journal. While Campath-1H did not eradicate Eleanor's Wegener's Granulomatosis, it provided a major turning point in her disease, allowing her 'to lead an incredibly full and rewarding life', which she continues to this day. Click here to see more on Eleanor's experiences.

Some of the acute problems Lockwood's patients were experiencing when he came to treat them with Campath-1H are captured by the case of John. He had first become ill in May 1998, and by the time he was admitted to Addenbrooke's Hospital, in October 1998, the blood vessels in his limbs had been so damaged that half of both his left leg and left arm needed amputation. John was given Campath-1H by Lockwood for six hours daily for ten days. Thereafter, his health began to improve. While not enough to reverse the damage in his right foot, resulting in him losing part of it, Campath-1H halted the spread of any more damage to the rest of his body. Since his treatment, John continues to lead as normal a life as possible to this day. Click here for a testimony of John's experiences written by his wife.

This photograph was taken of John watched by his wife in a chair while he was being treated at Addenbrooke's Hospital Credit: Millie Brierley.

Over the years Lockwood treated many patients suffering from various forms of auto-immune disorders with Campath-1H. All the patients were desperately ill at the time of treatment. Not all of the patients Lockwood treated with Campath-1H benefited from the drug. Click here to see the case of Linda, who soon after receiving Campath treatment died from her underlying disease. Lockwood's work with Campath-1H was cut short when he died in a tragic sailing accident in 1999.

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