Disconnect Observed Between Radiographic Progression, Disease Activity With Adalimumab in PsA

In patients with psoriatic arthritis (PsA) treated with adalimumab, a disconnect has been demonstrated between disease activity and radiographic progression. In addition, inhibition of radiographic progression was greater than anticipated based on control of clinical disease activity alone, according to the results of an ad hoc analysis (ClinicalTrials.gov identifier: NCT00646386) of the randomized double-blind placebo-controlled ADEPT trial published in Rheumatology.

The investigators sought to assess the relationship between radiographic progression and disease activity in participants with PsA who were treated with adalimumab or placebo, as well as the effect of concomitant methotrexate therapy. All participants were grouped according to time-averaged disease activity (ie, remission, low, moderate, or high), based on Disease Activity Score of 28 joints with C-reactive protein (DAS28-CRP), Disease Activity Index for Psoriatic Arthritis (DAPSA), or Psoriatic Arthritis Disease Activity Score (PASDAS), along with achievement of minimal disease activity (MDA) at 24 weeks. In addition, radiographic progression was evaluated as change in modified total Sharp score (mTSS) from baseline to 24 weeks.

The analyses assessed the following parameters: interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in patients categorized according to disease activity and treatment, and correlation between disease activity and radiographic progression based on treatment.

Results of the study showed that the interaction terms for time-averaged disease activity and treatment on mTSS were both statistically significant (P =.002 to P =.008). Regardless of concomitant methotrexate treatment, mTSS was lower with adalimumab vs placebo in all categories of disease activity. Of note, even in patients with moderate or high disease activity or patients not attaining MDA, mTSS was significantly lower with adalimumab compared with placebo (P <.05 to P <.001 for time-averaged DAPSA, time-averaged PASDAS, and MDA). Moreover, associations between time-averaged disease activity scores and mTSS were moderately positive and statistically significant (P <.001) with placebo but were not significant with adalimumab.

The investigators concluded that in patients with PsA, disease activity was linked to radiographic progression in patients receiving placebo but not in patients treated with adalimumab. In other words, adalimumab inhibited radiographic progression to a greater extent than might be expected based on the control of disease activity alone, which was not related to concurrent methotrexate use.

Additional studies are warranted that explore the long-term effects of the disconnect phenomenon described and thus comprehend its underlying mechanisms.

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Reference

Landewé R, Ritchlin CT, Aletaha D, et al. Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity [published online January 3, 2019]. Rheumatology (Oxford).  doi:10.1093/rheumatology/key417