SAN DIEGO -- The American College of Rheumatology annual meeting included 12 late-breaker poster presentations. Here are short summaries of the top six, according to our editorial opinion. Links to the abstracts are included (in two cases, to the full poster as made available by the sponsor).
Peptide Injection for OA
Four weekly doses of 23-residue peptide derived from matrix extracellular phosphoglycoprotein, injected into the knee joint in osteoarthritis (OA) patients, led to reductions in pain and improvement in knee-related quality of life and activities of daily living lasting a full year in a phase II trial, researchers reported ().
Action Points
- Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Called TPX-100, the agent is being developed by Orthotrophix, based in Oakland, California, which sponsored the current study.
In the randomized, blinded, sham-controlled trial, 118 patients (median age 60, median BMI 29.2) were randomized to receive the injections of active drug or saline. The poster reported a per-protocol analysis of 93 patients.
Both treatment arms showed large improvements 3 months after the first injection in the study's main outcome measures, which were components of the Knee Injury and Osteoarthritis Outcome Score, relative to baseline. But these improvements dissipated in the saline-treated group over the following 9 months, whereas they were maintained in the active drug group.
Oral Kappa-Opioid Drug for OA
Another phase II drug trial in OA involved an oral drug stimulating the kappa-opioid receptor, dubbed CR845 by manufacturer Cara Therapeutics of Stamford, Connecticut ().
The double-blind trial randomized 426 patients 2:1 to CR845 or placebo for 8 weeks, including a 4-week titration period followed by 4 weeks of maintenance dosing.
It missed the primary endpoint -- superiority to placebo in daily pain intensity at week 8 in the index joint (hip or knee) -- but post-hoc analyses found that patients with hip OA titrated to the highest dose (5 mg twice daily) did obtain a significant benefit. A strong placebo effect was seen for the overall sample.
Cannabinoid Agonist for Dermatomyositis
A synthetic agonist for the type 2 cannabinoid receptor improved a range of symptoms in patients with refractory skin-predominant dermatomyositis in a phase II study sponsored by drugmaker Corbus Pharmaceuticals of Norwood, Massachusetts ().
The rationale is that the CB2 receptor controls innate immune responses and cytokine release involved in dermatomyositis, the investigators said.
In this 22-patient study, patients were randomized to the oral drug, anabasum (also known as JBT-101), for 12 weeks. Outcome measures included pain, sleep disturbance, fatigue, objective skin appearance and damage, and patient-reported global disease. For most of these, significant improvements were seen relative to placebo during the treatment period. The agent was also described as well-tolerated with a "favorable safety profile."
Also for OA, a Cathepsin K Inhibitor
For decades, drugmakers have been looking at cathepsin modulators as treatments for inflammatory disease. Swedish firm Medivir AB is the latest to take a swing, with a phase II study of cathepsin K inhibitor MIV-711 in patients with knee OA ().
Two daily oral doses (100 and 200 mg) were tested in the placebo-controlled trial. Approximately 80 patients were treated in each group for 6 months, with a primary endpoint of average knee pain over the full treatment period. Secondary outcomes included radiologic assessments.
The primary endpoint was not met, but the investigators noted trends favoring the drug in nearly all symptom measures. Also, there were significant reductions in femoral bone area progression with both doses and in the rate of cartilage loss with the 100-mg dose.
Another JAK Inhibitor in RA
Starting with tofacitinib (Xeljanz), the so-called JAK inhibitors have revolutionized rheumatoid arthritis (RA) therapy by offering an oral therapy with more selective immunomodulation than traditional disease-modifying antirheumatic drugs (DMARDs), and manufacturers continue to seek new entrants into this increasingly crowded field. Now comes AbbVie with upadacitinib, selective for JAK-1, in a 24-week phase III trial (one of six being conducted) for patients intolerant of or unresponsive to biologic agents ().
This three-arm study randomized about 500 patients to placebo or one of two doses of the active drug. Overall, upadacitinib at both doses was superior to placebo in the usual outcome measures including ACR20/50/70 responses and scores on the DAS28, CDAI and SDAI scales.
Generally the drug was seen as safe, with no excess risk of serious infection. But six patients taking upadacitinib developed pulmonary embolism and the reason was unclear, as platelet counts remained within normal ranges in these individuals. "The clinical significance of this finding awaits the results of the other phase III trials," the investigators stated.
Second Malignancies with RA Biologics
Biologic drugs used in RA have inconsistently been associated with increased rates of new-onset cancers, and some clinicians have therefore questioned the safety of these agents in RA patients with a previous cancer history. To determine whether this is a legitimate concern, researchers in Denmark analyzed national registry data for incidence of second cancers among patients receiving biologics ().
The upshot: among 642 RA patients with prior cancer history who subsequently received biologic agents, the risk of second malignancies was not significantly greater than among 1,348 cancer survivors with RA who never received biologics.
Mortality was also examined in the study. A significantly higher death rate was seen among patients receiving biologics before a primary cancer diagnosis, compared with never-users of biologics. Among those starting biologics after a primary cancer diagnosis, there was a weak trend toward greater mortality. "No clear conclusion can be drawn" from these findings, the researchers said.