PHILADELPHIA—Despite a large and ever-growing number of therapeutic options for our patients with psoriatic disease, it is not uncommon for us come across scenarios in which a patient’s response to therapy does not match our expectations and our shared goals for treatment.
Dr. Merola
We all have those patients—the ones whose joints improve with one drug, but they continue to have active psoriasis, and vice versa. We also all have those few patients who seem refractory to multiple—and sometimes seemingly every—therapy prescribed. At ACR Convergence 2022, Joseph Merola, MD, MMSc, an associate professor of medicine and dermatology at Harvard Medical School, Brigham and Women’s Hospital, Boston, discussed treatment strategies for these exact patients. As a triple board-certified internist, rheumatologist and dermatologist, Dr. Merola is uniquely positioned to share insights on this topic. He serves as the vice chair for clinical trials and innovation and is director of the Center for Skin and Related Musculoskeletal Disease, a combined clinic seeing patients with psoriatic diseases.
Is the Diagnosis Correct?
When patients don’t respond the way we’d like, sometimes we’ve got to go back and ask: Is the diagnosis correct in the first place?
Even with plaque psoriasis, a differential diagnosis needs to be considered. Dr. Merola shared the case of a young woman referred to his combined clinic with well-demarcated, erythematous, psoriatic lesions of the buttocks that weren’t responding to psoriasis treatments. Her rheumatologist assumed that her musculoskeletal symptoms were related to the skin lesions and was treating her with methotrexate and subsequent TNF inhibitor therapy for psoriatic arthritis and psoriasis, with no improvement in symptoms.
A skin biopsy revealed cutaneous T cell lymphoma.
“If there’s a disconnect, remember to rethink your diagnosis. If things aren’t behaving as you’d expect, think about a dermatology referral and skin biopsy as appropriate,” Dr. Merola advised.
In this patient’s case, fibromyalgia and cutaneous T cell lymphoma were the most likely diagnoses. The morphologic differential diagnosis for plaque psoriasis was reviewed, including such entities as nummular dermatitis, psoriasiform variants of subacute cutaneous lupus erythematosus, psoriasiform lesions reported in anti-TIFi-γ dermatomyositis, allergic or irritant contact dermatitis, lichen simplex chronicus and seborrheic dermatitis.
When it comes to inflammatory arthritis symptoms in psoriasis patients, “remember that psoriasis and other joint diseases aren’t mutually exclusive,” Dr. Merola noted. He shared examples of patients who had concomitant psoriasis and what was clinically more consistent with seropositive rheumatoid arthritis, Lyme disease and crystal disease presentations—PsA patients are at a nearly fivefold increased risk for gout.1
Dr. Merola spoke next to the importance of a thorough skin examination by the rheumatologist. “We often say that about 80% of patients with PsA present with skin before joint disease, and about 10 to 15% present with joints first before the onset of cutaneous psoriasis. I think that’s probably an overestimate.
“If we had the patient undressed and really went looking, we might find psoriasis in other locations, especially intertriginous/body fold areas.” ‘Inverse’ or intertriginous psoriasis may be found in the axilla, inframammary region, inguinal folds, intergluteal cleft, abdominal folds; it is also important to examine the nails.
“Inverse psoriasis is not uncommon. Up to 23% in our published series of almost 4,000 patients had inverse disease. And inverse psoriasis is one of the phenotypic subsets that increases the risk of developing PsA,” he continued.2,3
Divergent Skin & Joint Disease
“Remember, we can really only optimize a patient’s quality of life by optimizing both their skin and joint disease,” Dr. Merola said. If the joints are responding well to treatment but residual skin disease remains, depending on the severity, options include adding topicals, adding apremilast or switching biologic therapy to another that better targets skin lesions.
Adding topicals is a good choice for many with mild or moderate residual disease when the joint disease is otherwise well controlled, but glucocorticoid topicals have downsides. All come with the risk of skin atrophy, and different prescriptions for different areas of the body confuse patients and prescribers alike.
But Dr. Merola had some great news to share: “We now have two recently FDA-approved non-steroid topicals that don’t cause skin atrophy and can be used on skin anywhere, just once a day. Roflumilast cream is a once-daily topical phosphodiesterase-4 inhibitor (PDE4i) that also works particularly well in the intertriginous areas from recent data. Tapinarof cream is a once-daily aryl hydrocarbon receptor agonist that has also shown promising results.”4,5
Dr. Merola reminded us to familiarize ourselves with the primary data in psoriasis studies where robust head-to-head data are available; not just those from PsA trials. He elaborated, “A well-done, recent network meta-analysis showed that interleukin-23 inhibitors (IL-23i) and IL-17i worked best in terms Psoriasis Area Severity Index-75 (PASI-75) and even PASI-100 (100% clear skin); these are some of our highest efficacy agents.”6
He drew attention to a new TYK-2 inhibitor, deucravacitinib, as an oral option. It has demonstrated superior efficacy and tolerability to apremilast in clinical trials for psoriasis.
Dr. Merola also highlighted two head-to-head trials comparing IL-17i inhibitors (i.e., ixekizumab and secukinumab) to a tumor necrosis factor inhibitor (TNFi), adalimumab.7,8 “What you see at high level are very similar joint efficacy outcomes, but superior outcomes with the IL-17i for skin disease,” he noted. “So in a patient with severe skin and joint disease, I would absolutely consider using IL-17i as first-line biologics in lieu of TNFi.”
Combo Biologic Therapy?
Dr. Merola touched on the emerging idea of combination biologic therapy. “This isn’t something we routinely do,” he shared, “but I want to introduce this idea for really severe and refractory cases. Many of our newer agents offer more targeted mechanisms with favorable safety profiles that should allow us to consider this approach for patients in need.
“Our colleagues [who have patients with gastrointestinal disorders or inflammatory bowel disease (IBD)] are doing some interesting work in this area. In the recent VEGA study, patients with moderate to severe ulcerative colitis were treated with a combination of guselkumab (IL-23i) and golimumab (TNFi), compared with biologic monotherapy. Those on combination therapy achieved higher rates of clinical response, clinical remission and endoscopic improvement by week 12, with no obvious safety signal in early data.9
“Similar work is ongoing in this regard for PsA and will hopefully inform our ability to consider combination approaches in the future.10 We have several patients with TNF-inhibitor-dependent IBD who develop psoriasis, TNF-induced psoriasis, PsA and other conditions for whom we have had tremendous success adding anti-IL12/23 or anti-IL23 to their TNF inhibition.
“I’ve also treated a patient with a combination of IL-17i and a Janus kinase inhibitor who had variably failed every mechanism for skin vs. joint disease and has only been able to capture both with combination therapy. This is obviously a single case, and we had to counsel her at length about the possibility of severe infection and other potential for long term side effects, but she has seen great response and has regained her ability to work and function. We envision utility of combination therapy as potentially an ‘induction regimen’ for flare-based control or for those truly resistant cases.
“This might become more of a reality in our PsA patients in the future. … Sometimes, you have to kill two birds with two stones,” he concluded.
Samantha C. Shapiro, MD, is the executive editor of Harrison’s Principles of Internal Medi-cine. As a clinician educator, she practices telerheumatology and writes for both medical and lay audiences.
