Predicting response to adalimumab
A prospective, multicenter, observational cohort study of 544 psoriasis patients on adalimumab monotherapy conducted by U.K. investigators concluded that a patient’s serum drug level is the single most important predictor of treatment response. A cut point of 3.2 mcg/mL, which is considered the minimal effective circulating drug level, was associated with a 65% probability of a 75% improvement in Psoriasis Area and Severity Index from baseline, or PASI 75 response. The higher the serum drug level, the greater the likelihood of a PASI 75 response, up to a serum level of 7 mcg/mL, which was associated with an 81% probability of achieving PASI 75. Beyond 7 mcg/mL, however, the relationship with treatment response plateaued. Importantly, drug levels measured early on – at 1-12 weeks into therapy – were predictive of response 6 months later. So were steady-state levels (J Invest Dermatol. 2019 Jan;139[1]:115-23).
This is clinically useful information, Dr. Duffin observed.
“I’m hoping we’re going to see more real-world use of checking drug levels,” she said.
Indeed, even though the approved dosing of adalimumab for psoriasis is 40 mg by subcutaneous injection every 2 weeks, the new American Academy of Dermatology/National Psoriasis Foundation joint guidelines for treatment of psoriasis with biologics declare that “a maintenance dose of adalimumab at 40 mg/week is recommended for better disease control in some patients” (J Am Acad Dermatol. 2019 Feb 7. doi: 10.1016/j.jaad.2018.11.057. [Epub ahead of print]).
The new guidelines provide support for dermatologists who decide weekly therapy is best for a given patient, and adalimumab drug levels could prove useful in identifying the patient subgroup likely to benefit.
Dr. Duffin is often consulted by other physicians as to whether they should check for neutralizing antibodies in patients who appear to be losing therapeutic efficacy on a given biologic. She’s not a fan of the practice.
“There are commercial assays out there, but it’s very hard to interpret them because we don’t really know if they’re truly measuring neutralizing antibodies. And the cost is not insignificant; it can be hundreds of dollars,” she noted.
She believes a straightforward measurement of the serum biologic level is a better strategy.
“It makes sense: This is an indirect way of determining if there’s been neutralization of the drug, rather than trying to check the antibody that’s doing it, which is fraught with problems,” Dr. Duffin said.
Radiographic progression and clinical PsA activity on adalimumab don’t always correlate
A post hoc analysis of the randomized, double-blind, placebo-controlled ADEPT trial in PsA patients demonstrated that inhibition of radiographic progression as measured by change in modified total Sharp score from baseline through 24 weeks of adalimumab therapy was greater than expected based upon control of clinical disease activity (Rheumatology [Oxford]. 2019 Jan 3. doi: 10.1093/rheumatology/key417. [Epub ahead of print]).
One implication of the disconnect between radiographic progression and clinical disease documented in this study is that a dermatologist shouldn’t be too quick to change from adalimumab to another biologic just because a patient with PsA reports continued but bearable joint pain. And the converse is also true.
“I think that we as dermatologists probably shouldn’t be reassured when a patient says, ‘My joints feel great!” That’s because you may not necessarily be able to predict lack of progression in Sharp score based upon clinical response,” Dr. Duffin cautioned. “I think you should still have a rheumatologist check in with the patient and do x-rays periodically. The rheumatologist I work with does that, usually about on a yearly basis.”
Another key finding in the ADEPT analysis was that concomitant methotrexate had no added effect in terms of preventing joint destruction. This underscores the prescience of the first-ever collaborative American College of Rheumatology/National Psoriasis Foundation guidelines for the treatment of PsA (Arthritis Care Res (Hoboken). 2019 Jan;71[1]:2-29).
The new guidelines recommend that, in a psoriasis patient with confirmed PsA, the first-line treatment is a tumor necrosis factor (TNF) inhibitor. Agents from this class are preferred over other biologics because they are backed by a larger body of data regarding inhibition of joint disease progression. If the patient fails on the first TNF inhibitor prescribed, second-line therapy is another TNF inhibitor. So is third-line therapy.