Rates of Cancers and Opportunistic Infections in Patients With Psoriatic Arthritis

K.W. Hagberg and colleagues published a very interesting and needed study: “Rates of Cancers and Opportunistic Infections in Patients With Psoriatic Arthritis Compared With Patients Without Psoriatic Arthritis.” They looked at a cohort of patients and compared them to matched controls “to assess the incidence of cancers (solid, hematologic, and nonmelanoma skin cancer) and opportunistic infections”. The results are important for decisions in treatment.

Conclusions: “The rates of solid and nonmelanoma skin cancers were similar in patients with PsA compared with patients without PsA, but the rates of hematologic cancer and opportunistic infections were higher in patients with PsA. In patients with PsA, rates of all outcomes were higher among those who received prescriptions for systemic PsA therapy.”

But let’s have a closer look.

The PsA cohort showed a higher rate of hematologic cancer than the non-PsA cohort. The highest  incidence rates ratios (IRRs) were in the group of patients under immunosuppressants (IRR: 6.79); patients under DMARDs and biologics (IRR: 3.59) and patients under other drugs (IRR: 3.50) showed comparable IRRs.

The rates of solid cancer and nonmelanoma skin cancer were similar in both the PsA and non-PsA cohort. The highest IRR has been estimated for patients under corticosteroids (IRR: 4.19).

The IRs (incidence rates) for opportunistic infections were higher in the PsA group. Patients under drugs (e.g. NSAIDs), DMARDs/TNFi or immunosuppressants showed IRRs from 1.65 to 1.88, patients under corticosteroids showed an IRR of 5.07 however. If you look at the results of the German registry for biologics in RA patients (RABBIT) you also find the highest rate of infections in patients treated with corticosteroids with a clear dose dependency.

My conclusion: in patients with psoriatic arthritis we need to be very cautious with corticosteroids.

Link:

K.W. Hagberg and colleagues: “Rates of Cancers and Opportunistic Infections in Patients With Psoriatic Arthritis Compared With Patients Without Psoriatic Arthritis.” J Clin Rheumatol. 2016 Aug;22(5):241-7. doi: 10.1097/RHU.0000000000000364. http://www.ncbi.nlm.nih.gov/pubmed/26886439

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Synavive (CRx-102) at the EULAR 2012?

Last year I had tweeted on Synavive, a combination of 2 mgs of prednisolone and 200 mgs of dipyramidole: “Zalicus has started a hhase [phase] 2b trial in rheumatoid arthritis; it's a glucocorticoid/dipyramidole combination. I still have my doubts! #rheum“.


Synavive had been presented at the ACR 2004; poster title: "Synavive (CRx-102) a novel, orally available, syncretic agent with significant in vitro and in vivo immuno-modulatory activity, and a dissociated steroid profile".
A poster with the title: “Phase 2 Trial to Investigate Synavive (CRx-102) for the Treatment of Active Rheumatoid Arthritis” (unclear, where it has been published) stated: “CRx-102 produces a clinically meaningful and rapid decrease in disease activity as assessed by DAS28, ACR and CRP in this 6-week study”.
At the EULAR 2007 another poster has been presented: “Inhibition of Macrophage and Chondrocyte Inflammatory Mediators by Synavive (CRx-102), a Novel Synergistic Combination Drug Candidate”.


And what did I hear at the EULAR 2012 in Berlin – nothing at all! So why am I writing on this topic? Because it could be an approach to reduce prednisolone dosage, it would be interesting to compare to Lodotra, and because it is discussed in non-medical circles (news for shareholders): “Zalicus has concluded patient enrolment in the Phase 2b trial of Synavive, a low-dose glucocorticoid used for the treatment of patients with rheumatoid arthritis (RA)”.


Maybe we didn't see anything new because of Novartis and Zalicus collaboration problems, but maybe this glucocorticoid/dipyramidole combination isn't a succeess story. I'll keep my eyes open at the next ACR and EULAR meetings.