As the ceremonies to mark the centenary of the 1916 rising come to a close, we reflect on some of the advances in psoriasis treatment that have occurred during this period. Until relatively recently, progress in the treatment of psoriasis had been steered by a succession of fortuitous accidental discoveries. A timeline for some of the most important of these chance findings (dithranol, methotrexate, vitamin D analogues and cyclosporin), is outlined below, beginning in 1916 when the effectiveness of dithranol was established. While these agents still provide valuable treatment options, their identification paved the way for a better understanding of the disease process and the development of more targeted therapies.
Dithranol (anthralin)
In 1876, Balmanno Squire (the chief of surgery and medicine for the British Hospital for Diseases of the Skin in London), reported the beneficial effects of Goa powder for the treatment of psoriasis. One of his patients had applied the powder to an area of ‘ringed’ psoriasis, which he mistook for ringworm, with good results. The active ingredient of Goa powder (obtained from the bark of the araroba tree found in South America), was found to be chrysarobin.
During World War I, when natural supplies of this product were scarce, a synthetic form called anthralin (dithranol) was developed. In 1916, it was demonstrated that anthralin was effective in the treatment of psoriasis, and it subsequently came into widespread use.
In 1953, British Dermatologist John Ingram, noted that the beneficial effects of anthralin could be enhanced by combining it with other ingredients (salicylic acid and zinc oxide), and exposure to ultraviolet light therapy.
Antimetabolites (Methotrexate)
Another chance finding was made in 1951, when Richard Gubner (a New York cardiologist) and colleagues, reported that a patient experienced a dramatic improvement in their psoriasis while being treated with a drug called aminopterin for rheumatoid arthritis. Aminopterin was originally used to treat patients with leukaemia. In 1958, methotrexate (a drug based on aminopterin, but with less risk of side effects) was shown to be effective for the treatment of psoriasis by American dermatologists, Edmundson and Guy.
Vitamin D Analogues
In the 1980s, Japanese researchers Marimoto and Kumahara, noted that a patient who was prescribed an oral form of vitamin D (1 , 25-dihydroxyvitamin D₃) for treatment of osteoporosis, experienced complete clearance of his psoriasis. This chance observation led to the development of topically applied vitamin D derivatives.
Cyclosporin
Cyclosporin is an immunosuppressant medication that was developed in the 1970s to prevent organ rejection in transplant patients. It was observed that when transplant patients who happened to have psoriasis were prescribed cyclosporin, their psoriasis improved. This observation helped to identify the important role played by T cells and more generally, by the immune system, in the development of psoriasis. This discovery paved the way for a better understanding of the disease process and for the development of more targeted therapies.
Recent scientific advances
During the last 2 decades, researchers have built on the knowledge gained from these chance findings, resulting in the development of new classes of medication that target the regulation of the immune system. A number of biologic agents have been licenced for the treatment of psoriasis including: tumour necrosis factor inhibitors (e.g. adalimumab, etanercept and infliximab), the interleukin (IL) 12/23 compound ustekinumab, and the IL 17A antagonist, secukinumab. These agents have significantly broadened the range and efficacy of treatment options available, and revolutionised the care of psoriasis patients.
The future
Over the last one hundred years, therapeutic advances have been informed by chance observations and scientific research. With studies on-going, more is being learned about the disease process and those insights are helping to shape the development of new medicines. For example, just last week, the U.S. Food and Drug Administration approved ixekizumab (a biologic that targets IL-17A), to treat adults with moderate-to-severe plaque psoriasis, providing another important treatment option. This new wave of improved, targeted therapies, heralds a new era in the treatment of psoriasis.
