Just 10 years ago, studies were being published on biologics for psoriasis, new promising steps forward. At that time, one author wrote that biologics “provide only modest efficacy compared with established treatments.” On the contrary, the past 10 years have marked an incredible period of change in the management of psoriasis. While some biologics have faded away due to efficacy and safety limitations, head-to-head trials and clinical experience have demonstrated the life-changing greater effectiveness of the new treatments that have been developed.
The pace of development of new treatments for psoriasis seems to have only accelerated. This issue of the Journal
of Drugs in Dermatology presents studies looking at new treatment approaches for both localized and more generalized psoriasis. For patients with relatively limited disease, Wong and colleagues present information on the use of 308 nm laser used in conjunction with topical agents. Their case reports suggest the possibility of combining these treatments to achieve both rapid improvement in the disease and improved long-term control.
With their high efficacy for both cutaneous and joint manifestations of psoriasis and their now established long-term safety profile, tumor necrosis factor (TNF) inhibitors have revolutionized psoriasis management. I have become accustomed to patients with severe psoriasis returning with big, bright smiles on their faces, proudly announcing how their treatment has been “life changing” for the better. One limitation of these products, however, has been the potential for loss of efficacy. Abuchar and colleagues report their experience
of etanercept re-treatment in patients who had documented loss of etanercept efficacy, finding a high percentage of patients achieving treatment success. The mechanism by which efficacy can be lost and then regained is not yet well defined, but the findings are consistent with my pet mechanism for treatment failure,
poor adherence to treatment. Perhaps many people believe that given the devastating impact of severe psoriasis, the effectiveness of TNF inhibitors in treating psoriasis, and the convenience of self-administered treatment that adherence would not be an issue. Yet adherence is still a hurdle, even for such highly effective
treatments. Looking on the bright side, this is probably a very good thing, because adherence is something that physicians can easily address to promote better treatment outcomes.
Several of the articles in this issue address the use of ustekinumab. Given the previous long draught of new, highly effective treatments for severe psoriasis that ended with the introduction of TNF inhibitors, it is startling
to me how quickly another major advance in psoriasis became available. IL-23 inhibitors are shaping up as very safe, very effective, and very convenient psoriasis treatments, albeit, like other biologics, expensive.
The PEARL trial reported here found dramatic improvements in psoriasis and in the quality of life of patients with psoriasis treated with ustekinumab. Famenini and Wu describe what we know about the safety of ustekinumab. So far, it looks terrific. So far. Will the safety profile hold up over time, or will we begin to see rare severe side effects of the type that killed efalizumab? While I often lean toward the pessimistic side regarding future safety findings of highly potent treatments, in this case I'm optimistic and don't expect any worrisome safety signal to develop given the apparently relatively benign nature—aside from Mycobacteria and Salmonella infection— of genetic deficiency of IL-23.
Lui and colleagues report the results of a study of the combination of alefacept with narrow band UVB treatments. Illustrative of how fast the field of psoriasis management is changing, alefacept is no longer available in the United States, out with 8-track, dial telephones, and, pretty much, stand-alone video stores. While I find downloading videos
over the web to be entirely satisfactory, I am sorry to see alefacept go, as it offered what seemed to be a very safe treatment option that was very effective for... um, for... well, for the people for whom it worked really well.
It looks like the innovations will continue. Kwatra and colleagues describe another promising approach to psoriasis management, a new class of oral anti-inflammatory treatments based on inhibition of Janus kinase (JAK). A highly effective, safe oral agent would be a welcome addition to our treatment options, as patients who have never experienced injection treatment would prefer not to have the experience. JAK inhibition interferes with signaling of multiple interleukin pathways, thereby providing a means to inhibit immunity without the hepatic and renal toxicities associated with methotrexate and cyclosporine. Will the oral JAK inhibitors have a broad safety window or will this form of immune inhibition be associated with a high risk of opportunistic infection? The future will tell.
Steven R. Feldman MD