No increased risk of solid cancers in PsA patients treated with TNF inhibitors
A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.
The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.
“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.
Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”
“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
Greater efficacy for biologics in males than females with PsA?
A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.
“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”
This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.
“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.
Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”
“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.
Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.